Final Flashcards
Why is cytomegalovirus dangerous when it comes to organ transplantation
It is the number one cause of disease and death in transplant patients
Infection in transplant patients of the cytomegalovirus can lead to what?
Pneumonia
It is a common complication of bone marrow transplant patients since disease is due to immune response
What complication does the cytomegalovirus cause in AIDS patients?
Blindness
What are the treatment methods for cytomegalovirus (CMV)
Ganciclovir
Foscarnet and cidofovir
What kind of virus does the cytomegalovirus have?
There is no vaccine
What is the diagnosis for the cytomegalovirus (CMV)
Serology for the primary infection
Viral isolation
PCR
Why is viral isolation hard for the cytomegalovirus (CMV)
It is the slowest growing herpesvirus so diagnosis takes about two weeks
What are the symptoms of the human herpesvirus 6 (roseola)
High fever with a rash for two days
What are the major complications with the herepesvirus 6 (roseola)
Encephalitis since it can replicate in the brain
What is the treatment for human herpesvirus 6 (roseola)
There is no treatment since rash is usually mild. There is also no vaccine for is as a result
What does the human herpesvirus 7 infect?
CD4+ T cells
What latent persistent viruses play a role in tumor formation?
Human papilloma virus and gamma herpesvirus
What chronic persistent virus plays a role tumor formation
Hepatitis B virus and hepatitis C virus
What is cancer?
Abnormal or uncontrolled growth
What is an oncogene
A gene that has been mutated given the ability of transformation in the cell, thus leading to abnormal division and growth of the cell
What is a proto-oncogene
The normal version of a gene that if mutated has the potential of causing abnormal cell growth and become an oncogene
What is a tumor suppressor
A protein that inhibits growth to prevent abnormal growth of the cell
Name the two common tumor suppressors
pRB which inhibits progression through the cell cycle (retina blastoma)
P53 which can cause apoptosis of the cell if there is DNA damage
What tumor suppressor mutation is on of the largest seen in human cancer?
P53
What is transformed cell
A cell that becomes a cancerous one due to some kind of mutation
What are the steps in organisms toward oncogenesis
Initiation, promotion, and progression
You generally need a lot of mutations for the cancer to arise
How is oncogenesis promoted in cell culture?
Immortalization, then transformation
Can acute viruses cause cancer?
Generally, no
What are the two methods that a virus can cause cancer
Direct and indirect method
What is the direct way that a virus can cause cancer?
By carrying an oncogene that is transcribe with it in the cell
What is the indirect method for viral infection causing cancer
Chronic viruses can cause constant death and regeneration of cells that normally do not divide lead to an accumulation of mutations
Retrovirus genome insertion next to an oncogene can alter regulation
Very slow
Why are chronic viruses dangerous
Constant death of cells in tissue causes constant regeneration which can lead to an accumulation of mutations in the cells which can lead to too many mutations causing cancer.
Liver is especially dangerous because it has rapid regeneration
What direct viruses encode an oncogene
Retrovirus (Roy’s sarcoma virus)
Small DNA virus (HPV, MCPyV, SV40)
Large DNA virus (herpesvirus)
Why do viruses evolve to interact with tumor suppressors
Activate cellular machinery so that replication of virus can begin
It will also block programmed cell death so that the virus can survive
How is the papillomavirus maintained in the human
As an episome
What does the human papillomavirus cause?
Warts
Describe the spread of the human papilloma virus
On skin, usually when there are cuts on the fingers, wart can appear
Genital warts are spread sexually
What is the major problem with the human papilloma virus
The are a major cause of cervical cancer
What virus is associated with head and neck cancer
Human papilloma virus
How would someone get throat cancer?
Oral sex, it is made worse by smoking
Describe human papilloma virus replication
Virus replicates in the spinous layer on skin (where all early genes are expressed) The no dividing cells where the particles are released in the upper layers (where late genes are expressed)
Where is the human papilloma virus latent
In the basal level cells where early early genes are expressed
Describe the treatment for warts
Cryosurgery and laser treatment for removal of the wart
You can also use immune activators, salycilic acid treatment
What is salycilic acid treatment
Killing the skin in the wart area to kill all of the virus
What is the fourth leading cause of cancer death in women
Cervical carcinoma
What external factor exacerbates cervical cancer?
Smoking
How does HPV cause cervical cancer?
It causes an abnormal expression of E6 And E7 in the basal andsuprabasal layers of the skin leading to abnormal cell growth and ultimately cervical cancer
E6 prevents p53 from working
E7 promotes pRB in the cell in order to increase cell cycle
What is the HPV vaccine
Gardasil, it contains a single capsid protein to generate an immune response
This is given to women and girls
Now it can be given to men
Has 4 strains and gardasil 9 has 5 new strains added
What tumor viruses are associated with the gamma herpesvirus?
Epstein bar virus (EBV)
KSHV
Herpes Virus saimiri
What kind of virus is the Epstein Barr virus?
A gamma herpesvirus
What kind of infection does the Epstein Barr virus establish?
Life long latency
What is a major complication with the Epstein Barr virus?
Cancer due to its life long latent infection
It also cause infectious mononucleosis
What are the symptoms of mononucleosis?
Sever fatigue
Sever lymphadenopathy
Slenemology, lasting about a month
What is responsible for the disease caused by mononucleosis, caused by the Epstein Barr virus?
Expansion of Bcells and Tcells
Fatigue could be due to cytokines release
What age group does mononucleosis affect
Usually teens but not children
Children are usually a symptomatic
Where is burkeitts lymphoma endemic?
Africa, usually in children too
Areas with high malaria rates
What causes burkitts lymphoma
Epstein Barr virus in all of African cases, but only for half of the cases in North America
What does burkitts lymphoma require in order to produce the cancer
C-myc chromosomal translocation leading to over expression of an oncogene
What diseases does the Epstein Barr virus cause?
Burkitts lymphoma
Nasopharyngeal carcinoma
Lymphoproliferative disease
What is nasopharyngeal carcinoma
Infection of epithelial cells caused by Epstein Barr virus
Who does the lymphoproliferative virus infect?
Usually immunocompramised patients and people with HIV
What cells does the Epstein Barr virus infec (EBV)
Epithelial cells and resting B cells in the oral cavity
How does the Epstein bar virus become cancerous?
Translocation of the viral genome next to c-myc site that causes An increase in cell proliferation. This usually happens in the epithelial cells and rarely B cells
What kind of infection of the Epstein Barr virus in epithelial cells happens?
Latent and lyric infection
What kind of genes does the Epstein Barr virus express to promote oncogenesis?
It has 10 genes expresses and of those, LMP1 acts as an oncogene in cultured cells because it prevent s apopotosis
What are the symptoms of EBV
Fever, pharyngitis, lymphadenopathy, splenomegly
What is the diagnosis for EBV
Look for an increase in the total lymphocytes
Serology, look for heterophilic antibodies and EBV specific antibodies
What is the treatment for EBV
Moral support, HSV treatments do not work well
What is kaposi’s sarcoma?
Tumor caused by gamma herpesvirus
What is the most common tumor in AIDS patients
Kaposi’s sarcoma, a gamma herpesvirus
Where is KS endemic (kaposi’s sarcoma)
Sub Saharan Africa
Most common reported tumor overall in some countries
During the latency stage of the herpes simplex virus, what is made?
Latency associated transcripts
• Describe the latency associated transcripts of the herpes simplex virus
o There is no protein made from this and the t-cells cannot target any protein to create an immune response against the virus
o These are turned into microRNAs
• What is the role of the latency associate transcripts?
o It blocks apoptosis of the cell
• What are microRNAs
o Small regulatory RNAs
o An example is Latency associated protein
• What is the problem with the immune response targeting the herpes simplex virus?
o There are no proteins for the immune system to target allowing the cell to remain in the latent state
o T-cells only respond during the reactivation phase of the virus
• When are t-cells activated against the herpes simplex virus?
o When the virus is reactivated but not in the latent state
• Other herpesviruses that are lateen in dividing cells make proteins to maintain the viral genome as an episome when cells divide, why does HSV not need to do this?
o Because the herpes simplex virus infect non dividing cell (neurons) therefore there is no need for it to maintain itself during replication
• What is the difference between the lytic and the latent state of the herpes simplex virus
o In lytic state, over 80 genes are expressed while in the latent state, only one gene is expressed
o In the lytic state the virus replicates rapidly through the use of the host machinery while in the latent state there is no replication happening because the herpes simplex virus infects non dividing cells (neurons)
o In the lytic state, the infected cell dies while in the latent state, the infected cell is alive until reactivation toward the lytic state
o In the lytic state, the virus cause lesion in the lips and genitals while there is no disease created during the latent state
o In the lytic state, there are antiviral drugs that can inhibit the replication of the herpes simplex virus, while during the latent state, there are no drugs because there is nothing to target
o In the lytic state the immune system will eventually shut down the virus, but in the latent state because there is nothing for the immune cells to target, there is no immune attack on the latent herpes simplex virus
• How is the herpes simplex virus reactivated?
o Stress, UV light, fever, hormonal changes, menstruation
• How does the herpes simplex virus reactivate?
o Upon activation, the virus will initiate lytic replication inside the neurons. This infection will then travel from the neuron to the original site of the lesion and begin to spread to other cells causing more lesions
• How does the herpes simplex virus affect immunocompromised patients?
o The sores upon reactivation become very large and cover most of the skin
How much of the herpes simplex virus gets reactivated during the reactivation stage?
Only a small percent
What is a major complication of the herpes simplex virus?
Encephalitis, but this is very rare
How can the herpes simplex virus cause encephalitis?
Upon reactivation of the virus, the virus can travel in the opposite direction and infect the brain instead where it will then replicate. This leads to encephalitis and ultimately death if untreated
How is the herpes simplex virus diagnosed?
You can take skin scraping of the legion and grow the cells in culture in order to isolate the virus
You can also isolate the virus from cerebral spinal fluid in order to detect encephalitis
PCR of spinal fluid (spinal tap)
Check for antibodies in pregnant women to see if the women has had the infection before
What is the treatment for the herpes simplex virus?
Antiviral chemotherapy. This is Acyclovir drug
How does Acyclovir work?
It is treatment for the herpes simplex virus and it works by phosphorylating the viral thymidine kinase. This will then be incorporated in the DNA chain and the incorporated acyclovir will then terminate the ongoing DNA chain
This only works on the lytic virus
Generally, it blocks the replication cycle of the herpes simplex virus
What is the prevention method for the herpes simplex virus?
There are no vaccines for the herpes simplex virus
Use of condoms
Taking Valtrex
Describe the basic principles of the Varicella Zoster Virus (VZV)
It is a herpesvirus and it is the cause of chicken pox
What is the major problem with reactivation of VSV?
The person can get shingles
Describe shingle
Extremely painful reactivation of the third herpes virus. It is a neuronal disease that usually spreads from shoulder to the groin
Can someone get the shingles virus from a primary infection?
No
Describe the Varicella Zoster virus infection
Same replication cycle as HSV
Initial infection becomes disseminated
What is the major complication with the Varicella Zoster virus?
It can also cause encephalitis but like in HSV, this is very rare
Where does the Varicella Zoster virus establish latency?
In the neurons of the trigeminal and dorsal root ganglia for life of the host.
Reactivation usually happens only once
What is the most infectious human herpesvirus?
Varicella Zoster virus (VSV)
Describe the spread of infection by the Varicella Zoster Virus
It is spread through the respiratory route.
Where does the infection of the varicella Zoster (VSV) spread?
Infection will begin at the upper respiratory tract where it will the disseminate through the body via the bloodstream
Can shingles be spread?
No it can only come up upon reactivation of the latent state of the primary infection of the Varicella Zoster virus
Describe VSV dissemination within the host
First the infection begins in the upper respiratory tract where the virus will then replicate in the lymph nodes. Then the virus will spread as primary viremia allowing the virus to replicate in the liver, spleen and other organs. Then the virus will continue as secondary viremia leading to infection of skin and vesicular rash
Describe the diagnosis of VSV
Basically you can look at the symptoms since they are very distinct You can also use lab diagnosis Elisa for antigen Culture the virus In situ hybridization
Describe the treatment for Varicella Zoster virus
You can use antibody therapy to make the disease shorter
For high risk cases, you can use Vzig
Acyclovir can also be used
What is the prevention method for VSV?
There is a live attenuated vaccine called “Oka” that is given to infants
What are the problems with use of the VSV vaccine?
There is a potential danger that the future vaccinated children, when adults can become susceptible to the virus because the long term future is still unknown for the capabilities of the vaccine
Describe the Herpes B virus
This is an alpha herpesvirus that is found in Macaque monkeys
This spread to humans through zoonotic infection during handling of monkeys
There was only one case of human to human transmission.
Why is the cytomegalovirus most common on the 2nd child?
the first child brings home the virus from school
What virus is the most important cause of congenital viral infection in the US
cytamegalovirus (CMV)
How is Cytomegalovirus spread?
usually by saliva but can be spread through blood
also breast milk, saliva, sexualy, urine, organ transplant, transplacental barrier
What can happen through prenatal infection of the cytomegalo virus
Deafness, brain damage, encephalitis, hepatitis
usually happens in the first trimester
Describe the pathogenesis of the cytomegalovirus
It will first infect mucosal epithelial cells where it will spread to leukocyte viremia and infect/establish latentcy in hematapoetic stem cells
What virus is the largest human herpesvirus?
cytomegalovirus
What kind of virus is the cytomegalovirus
Beta herpesvirus
has slow lytic growth
What is the treatment for parvovirus B19
antiinflamatories to prevent arthritis
blood transfusion for anemic patients
What is the diagnosis for parvovirus B19
Serelogical assay for IgG
PCR assay
What genes are expressed during the various phases of HSV Gene expression
Intermediate early genes-regulatory genes
Early genes-replication genes
Late gene-structural genes
Describe the epidemeology of the parvovirus
It has a world wide prevelance and most people actually get this
What is the biggest complication with parvovirus infection of the fetus
Miscariage
leads to severe anemia which can cause hydrops fetalis leading to fluid build up in fetus
Why is the parvovirus dangerous for pregnant women
It can cross the placental barrier
Why does a rash arise in the parvovirus infection?
immune system
at this point the patient is not infectious
What are the symptoms of the Erythema infectiousum
Redness in skin
mild rash on cheeks
mild arthritis in adolescents
anemia in immunosuppressed patients
What is it called when the parvovirus infect erythroid lineage cells
erythema infectiousum
What cells does the parvovirus infect?
erythroid lineage cells of bone marrow that will become red blood cells
fetal liver cells
What does the parvovirus need in order to replicate
actively dividing cells
Compared to its adeno associated virus cousin, how is paravovirus B19 different
It can replicate on its own
What is the Rubella Diagnosis
Use IgM elisa for congenital infection for pregnant mother.
High IgM levels without IgG means further tests must be done on fetus
Virus isolation in cell culture
Rt-PCR
Why is is dangerous to give the rubella vaccine during child bearing years?
Possibility of infecting the fetus since IgM cannot cross the placental barrier
Describe the Rubella vaccine
Live attenuated vaccine
provides life long protection with little side effects
Describe the epidemiology of congenital Rubella Syndrome
Due to vaccine, occurance are rare in the united states
developing countries have lower vaccination rates so the occurances are higher
amish people do not get vaccines so it is more common for them
What can happen to the fetus if the mother has a primary infection of Rubella within the first 16 weeks
mental retardation cataracts heart defects premature delivery deafness not too common after first trimester
If Rubella is such a small infection, what is the major problem with it?
Congenital Rubella syndrom
What is the treatment for rubella
No treatment since the infection is usually mild
What is the uncommon symptom of Rubella childhood infection
mild encephalitis-headache-vomiting
Describe the childhood pathogenesis of Rubella
It first infect through spread by aeresol droplets infectin mucosa of upper respiratory tract
It will then travle by primary viremia to the lymph nodes where it will then spread to secondary viremia, where it will then cause rash from face to feet
What are the three types of mother to child transmissions
Intrauterine
Intrapartum
postnatal
What is the word for infection of the fetus during pregnancy
Intrauterine
What is the word for infection of the baby during the birthing process?
Intrapartum
What is the word for vertical transmission that happens after birth
Postnatal
Describe the intrauterin process. What must the virus do to infect the fetus
Virus must cross the placental barrier in order to access the fetus or else virus will be filterd out
virus can also ascend from the genital tract
What does the placenta do for the baby
separates mother and fetal blood so that it does not mix
What are the cell layers that separate mother and fetal blood? That create the placental barrier
Syncytiotrophoblasts
Cytotrophoblasts
basil lamina layer
What antibodies play a role in fetal immunity
IgG and IgM
What antibody in fetal immunity can cross the placental filter
IgG
What antibody in fetal immunity is too large to cross the placental filter?
IgM
Describe the role of IgG in fetal immunity
This can cross the placental barrier allowing the mothers antibodies to be passed to the fetus for protection
Describe the role of IgM in fetal immunity
It cannot cross the placental barrier because it is too large, therefore, during primary infection, there is no immunity from the mothers antibodies to the fetus
Why is reactivation of HSV in the mother much less dangerous to the neonate than primary infection
IgM antibodies are too big to cross the placental barrier, therefore, the virus can infect and cause harm to the fetus
What is the advantage and disadvantage to breast feeding
Virus such as HIV can be transmitted
you can get IgA antibodies this way
What are the possible complications with fetal infections
Brain damage mental retardation development problems spontaneous abortion deafness
How do fetal infections of the virus cause defects?
The virus will replicat in specific cell types causing destruction of important cells during development
How is HIV verticaly transmitted
transmission happems in utero, through blood, genital secretion, and breast milk
Why is HIV through vertical transmission dangerous?
The time between HIV to AID is greatly accelerated
What is a major complication of vertical transmission of the herpes simplex virus
Brain damage
What are the hosts for the rubella virus
human, no known childhood infector
mainly children
What are the symptoms of a rubella childhood infection?
Mild rash
low grade fever
lymphadenopathy
What is the drug used for HSV treatment
acyclovir
What does Acyclovir for HSV do?
blocks herpes simplex from replicating
What does the herpes simplex virus cause in human
facial of genital sores keratitis encephalitis herpetic whitlow disseminated sores in immunocompramised people and neonates
What is keratitis and what virus causes it?
eye disease and HSV
What causes herpes simplex lesions?
Virus infects muco epithelial cells, spreading cell to cell causing death and inflammation
forms single or multiple lesions that creates a small painful ulcer because it infects the neurons in this region. Virus is then cleared
To cause lesion, what cells do the HSV virus infect?
mucoepithelial cells
When a herpes simplex lesion is about to reoccur, what does a person usually experiance
a tingling feeling at the initial infection site
How is the herpes simplex virus spread?
direct contact through kissing
sexual transmission
finger cuts
vertical transmission
How is the herpes simplex virus spread through kissing
Direct contact because is allows HSV to infect the subcutaneous epithelial cells in the lip area
What is it called when a herpesvirus is obtained from finger cuts
hepetic whitlow
Describe the vertical transmission of HSV-2
The mother can pass to infant if she gets a primary infection. Reactivation usually does not lead to spread because the mother has antibodies to pass on to the child
birth canal with herpes lesions will most likely cause spread leading to brain damage and overall death
Is the herpesvirus usually symptomatic
no, asymptomatic
What is the problem with the spread of herpes?
most people are asymptomatic, so they can spread the virus without knowing that they actually are
What cells does the HSV infect and describe its pathway toward infection
Neurons are first infected by HSV around the epithelial cells leading to the virus traveling up the neuron and establishing latentcy
Where is latency established by HSV?
trigeminal or dorsal root ganglia
What is the bundle of neurons that innervates the face that is infected by HSV? What is the bundle that innervates the genitals?
trigeminal ganglia
dorsal root ganglia
When HSV establishes latency, What does the viral genome remain as?
an episome
What is the viral genome called when it establishes latency but does not insert itself into the genome?
episome
How does a persistant virus overcome elimination by the immune system
Immune evasion by counteracting host response
high mutation rates avid host in viruses such as HIV
resides in immuno privileged areas
latent state that limits gene expression to avoid immune system
What are the three types of viral infections?
acute
chronic
latene
What is an acute infection
virus replicates rapidly
virus is cleared 1-3 weeks
What is a chronic infection?
Virus is continuously shedding
infection lasts months to years or even lifetime
What is a latent infection
No viral shedding
limited gene expression
lasts for the lifetime of host
episodic reactivation
What viruses have a chronic infection
Hepatitis C/B
HIV
What viruses have a latent, reactivation
Herpes Simplex virus/ other herpes viruses
VSV (chicken pox)
Draw a production over time graph for a: chronic infection acute infection latent/reactivation infection slow virus
refer to flash card
What are the problems the acute virus must overcome?
Must find next host quickly since the body clears it fairly quickly
must spread easily
must not kill host quickly
Describe the polyomaviridae family
small, non-enveloped viruses
Name some polyomaviridae viruses
JC, BK viruses
SV40 the simian virus
Why is SV40 often studied?
Its role in transformation using the large T antigen
What is Merkel Cell carcinoma
a rare skin disease that is very deadly
It is thought to be caused by the polyomaviridae Merkel cell polyomavirus
What kind of patient is Merkel Cell Carcinoma (MCC) common in?
Immunosuppressed patients
What are the two liver cell types
Hepatocytes (main liver cell)
Sinusoids (thin walled blood vessels of the liver
What helps produce extra cellular matrix to provide structural support for the liver
Hepatic Stellate Cells, Hepatocytes and liver blood vessels
How does an acute liver injury affect the liver
the healing response to the wound disrupts the balance between the extracellular proteins and degradation of the proteins by the extracellular protease
How does a chronic liver injury affect the liver
there is an over expression of the extra cellular matrix that causes fibrosis of the liver
What causes cirrhosis of the liver?
fibrosis of the liver caused by an over expression of the extracellular matrix proteins
What is it called when there is a build up of scar tissue or extracellular matrix that block blood from getting to the liver?
Cirrhosis
Why is hepatocellular carcinoma a problem
Liver cancer is the third leading cause of death in the world
What is hepatocellular carcinoma?
Cancer of the hepatocytes, which is essentially cancer of the liver
What is the most common cause of hepatocellular carcinoma (HCC)
cirrhosis of the liver
What virus is the major cause of hepatocellular carcinoma?
Hepatitis B and C
What external factors can increase liver damage by hepatitis B and C
Alcohol, it can also cause hepatocellular carcinoma without actually being infected by the liver
Do the hepatitis viruses directly cause hepatocellular carcinoma?
No even though it contains an oncogene that can directly cause hepatocellular carcinoma (HCC)
What does the chronic hepatitis virus do tot he liver?
It causes constant cell death of the hepatocytes and the constant regeneration which can lead to mutations in the replication of the genome and ultimatly cancer
What increases the risk of cells becoming cancer
rapid multiplication caused by replication of cells from viral infections
Usually how long does it take for hepatocellular cancer to arise in patients with a chronic hepatitis virus
A very long time because you need an accumulation of mutations
Unless you drink alcohol, that makes it go faster
Describe the process of a chronic virus causing oncagenesis
The constant regeneration of cells due to cell death causes a high risk of mutation due to the need for rapid replication. This over time will lead to an accumulation of mutations that will eventually promote one cell to become oncogenic and thus causing cancer
What family is the hepatitis virus B in?
Hepadnaviridae
What is the structure of the hepatitis B virus?
Enveloped virus
What is unique about the hepatitis B virus?
It goes through an RNA stage making a DNA retrovirus
What virus is the most common cause of chronic liver infection?
Hepatitis B
What genes does the hepatitis B virus encode?
Pol (RNA and DNA dependent DNA) Core (capsid protein) S protein (surface antigen (envelope) HBV X (signal transduction and transcription factor) HBV e (secreted form of C protein)
Describe the process of Hepatitis B replication
Double stranded DNA enters the nucleus and then circularizes where ithe (-) DNA will make mRNA to create the coat protein. Then the RNA is reverse transcribed by the reverse transcriptase from the virus and then that DNA is packaged (The partiall double stranded DNA
What is the major rout of transmission of the Hepatitis B virus (HBV)
Sexual transmission
maternal to fetal
breast milk, blood, tear fluid
What bodily fluids can contain infectious hepatitis B virus?
Serum, urine, saliva, nasal secretions, vaginal secretions, and seman
What is more infectious if you accidentally used a contaminated needle, HIV or HBV
Hepatitus B virus, you have about a 40 percent chance of getting it, while for the HIV virus you have about a 0.3 %
What induce hepatitis when infected by the hepatitis B virus?
The immune system causes the damage on the liver
Does the Hepatitis B virus directly cause hepatitis to arise?
No it caused by the immune system, the Hepatitis B virus does not actually lyse the cell, it is an enveloped virus that just buds from the cell
Where does the Hepatitis B virus replicate?
In the hepatocytes in the liver
What HBV antigens appear in the serum during the disease?
HBV S protein (surface) HBVe antigen (soluble form of core protein that can be found in the blood
What happens to ALT and AST levels when the HBV DNA disappears
It increases and the patient will get jaundice
What is a major complication of the Hepatitis B virus infectioon?
Fulminant hepatitis (1%) and chronic hepatitis(5-10%) but this usually both happens in a small number of partients diagnosed in the virus
What is Fulminant Hpeatitis?
Acute liver failure which eventually leads to death and in rare cases is caused by the hepatitis B virus
How does a chronic infection of Hepatitis B virus arise, that generally leads to hepatocellular carcinoma?
If there is a lack of immune control that will generally lead to a chronic infection
-if the patient is immunosuppressed or a male
What is the major complication with Chronic Hepaititis B virus?
Cirrhosis and hepatocellular carcinoma
-This is usually accelerated with alcohol
What is one way to treat hepatocellular carcinoma?
liver transplant
What are the two direction toward disease that chronic hepatitis can become
Persistent hepatitis which can eventually lead to aggressive hepatitis, leading to cirrhosis
Describe the Diagnosis of the hepatitis B virus
You can use serology to analyze HBV S and C (the surface and the coat protein), you can also look for HBV A and HBV A in the blood at high levels (antibodies)
-You can also use genome amplification by doing PCR of the viral DNA in the blood or you can look at the amount of virus you have in the liver by doing a liver biopsy
Does the hepatitis B virus have a vaccine?
Yes
What does the Hepatitis B vaccine consist of?
recombinant hepatitis B surface antigen
How is the Hepatitis S antigen made for the hepatitis B vaccine?
purified yeast
How is the HBV vaccine administered?
there are three doses that is give at 0, 1, and 6 months
Why is a cure for the HBV virus hard to come create?
because the DNA of the Hepatitis B virus is circularized
What does the treatment for chronic hepatitis B virus consist of?
These are drugs used to decrease chronic replication of the virus but it is not a cure so it must be taken for a long period of time
- You can also use interferon Alpha treatment but it is not virus specific
- lamivudine (3TC) which is a a nucleoside analog Reverse transcription inhibitor
What is Hepaititis Delta
it is not a virus but a sub-viral particle because it does not have a viral attachment protein or a polymerase
Which hepatitis virus is not an actual virus
Hepatitis Delta since it does not have a virus attachment protein or a polymerase
What does HDV require to infect a cell
Infection by HBV since it borrow the envelope proteins of the HBV virus to move from cell to cell
What are the two patterns for hepatitis D virus infection?
Co-infection and super infection
Describe the co-infection of the hepatitis D virus
When both HBV and HDV infect at the same time
Describe the super infection pattern of the Hepatitis D virus
This is when HDV infects a previously chronically infected HBV patient
Why is a super infection pattern of HDV dangerous
It increases chances of getting a fulminant disease and it creates the presence of HBsAg causing an immediate spread of HDV in the body
Discuss the diagnosis of the hepatitis D viris
You can use serologic assay to look for Delta antibody -IgG and IgM and RNA from the virus
What is the treatment for the hepatitis D virus?
There is no treatment
Why is it hard to create a treatment for the hepatitis D virus?
Because the hepatitis B treatment does not target the Hepatitis S protein or production and HBV S is needed for HDV infection
What is the prevention method for hepatitis D
Use the hepatitis B vaccine
How was the Hepatitis C virus identified?
Through molecular biology methods and this was the first virus found this way
What family is the hepatitis C virus in?
flaviviridae
What is the Hepatitis C virus genus
Hepacivirus
How is HCV transmitted?
it is a blood borne virus
What is the leading cause of HCV?
injection drug abuse
What are the rare ways that hepatitis C may also be transmitted?
Hospital needles
tatoos
vertical transmission
Sexual transmission
What are the two types of HCV disease and which one is most common?
Acute and chronic infection and the chronic infection is more common
Describe the acute infection of the hepatitis C virus
HCV will replicate in the hepatocytes with symptoms usually being. mild or absent Jaundice may occur
Describe the chronic infection of hepatitis C
HCV will constantly replicate in the hepatocytes allowing for persistent viremia
-a mild disease willusually occur that will lead to inflammation of the liver and a mild increase in ALT
What increases the damage done by the hepatitis C virus
Alcohol and having a suppressed immune system
Discuss the epidemiology of the Hepatitis C virus
this is seen world wide
What is the most common cause for a liver transplant in the US
Hepatitis C
How many major genotypes of HCV is there
6
How is HCV diagnosed?
you look for HCV antibodies
you can also check for viral RNA in the blood through the use of PCR
-Here you cannot really look at ALT to determine how severe the case is
Discuss the treatment of HCV
You can use interferon therapy to treat the chronic infection
-you can also give a combination of both Pegylated IFN and Ribavirin
What is the problem with HCV drug therapy?
Nearly half of all the patients do not respond to the therapy and are therefore not cures
-also interferon and ribavirin have awful side effects such as malaise and flu like symptoms
What is the new drug used to cure HCV?
It is called Harvoni, which is a combo drug, that works as an inhibitor, and it uses NS5A inhibition
Discuss the difference in rates of chronic infection between hepatitis B and hepatitis C
Hepatitis C has an overwhelmingly large amount
What is unique about the hepatitis C virus
it is a blood borne hepatitis virus
What is unique about the retroviridae that is not seen in other viruses?
It is a diploid virus meaning it has two copies of its (+)ssRNA
Why is the retroviridae called retro?
Because the RNA must use a reverse transcriptase in order to make DNA from the RNA and then make the protein
Why do the retroviride go through the process of revers transcription?
So that it can incorporates its DNA into the DNA of the cell
What are the two types of Retroviridae?
Simple retrovirus and complex retrovirus
What viruses are under the category of simple retroviruses?
Alpharetrovirus
betaretrovirus
gammaretrovirus
What is unique about the genome of simple retroviruses?
It has long terminal repeats on each side that is needed for replication
What are the three genes made by the simple retrovirus genome?
gag: group associated antigens
pol: polymerase
env: Envelope
How does the retrovirus enter the cell?
Through fusion
What gene is involved in retrovirus entry?
Env which creates 2 subunits, which are the viral attachment protein and the fusion protein (
What is the retrovirus lipid envelop contain?
trimer which are 3 copies of hetero-dimers. The heterodimers areboth the SU and TM protein combined
Where does fusion occur for the retrovirus?
At the plasma membrane of in the endocytic vesicles
Describe the process of Retrovirus fusion
The SU protein will bind to the cell membrane where a hair pin will form by the trans membrane protein in order to allow fusion
What protein of the retrovirus allows for fusion?
The transmembrane protein
What is peculiar about the fusion mechanism of viruses?
It is conserved among other viruses
What Retrovirade protein allows for integration of the viral genome into the cell genome?
Integrase
What important virus particle must be packaged inside the retrovirade?
A reverse trannscriptase and integrase
In terms of infection what is the difference between the simple retrovirus and the complex retrovirus?
The simple retrovirus requires cell division
-The complex retrovirus can successfully infect on-dividing cells
When the genome is integrated into the host cell, what is this called?
provirus
What happens to a cell with a provirus during division?
During division that means the virus will replicate as well
Is the retrovirus site specific?
There are usually no specific target sites by the virus
What happens after retrovirus integration in the cell?
Transcription
How are the protein transcribed in the retrovirus
ASK
Describe the maturation process of the retrovirus
Gag is cleaved by the viral protease into separate protein after budding
What proteins are cleaved during the maturation of the retrovirus?
Matrix (ma)-lies underneath the lipid envelope
Capsid (CA) whcih forms the shell of the protein
Nucleocapsid (NC)
What makes a retrovirus not infectious?
When it has yet to undergo maturation
What did retrovirologists discover that became revolutionary to how we study genes?
The oncogene because the avion retrovirus carried an oncogene to induce carcinoma
What is the normal version of an oncogene called?
A proto-oncogene
what is it called when a cell becomes cancerous?
transformation
Describe the acute transforming retroviruses
This is when the retrovirus that infects a cell directly carries a proto-oncogene with it, most are defective
What makes a retrovirus defective?
Usually the gag or pol or env gene is replaced with an oncogene and it therefore requires another retrovirus infection to allow for the over-expression of the oncogene
How long is the time for tumor formation when infected with an acute transforming retrovirus?
usually weeks
Describe how the Non-transforming retrovirus causes cancer?
This induces cancer through indirect induction. The retrovirus is integrated near a proto oncogene causing the induction of an oncogene
Why is retroviral therapy a problem?
Because there is a chance of indirect induction of tumors where the retrovirus will integrate its genome at a proto oncogene
What makes up a huge portion of the human genome?
Human endogenous retroviruses
Can human endogenous virus be reactivated?
Very few can
What RNA viruses can causes cancer?
Retroviruses
What is HTLV
Human T lymphocyte virus
What kind of virus is the human T cell Leukemia virus?
A deltaretrovirus
What genes doe the Human T leukemia virus contain (HTLV)
Gag pol env tax Rex
What does the Tax protein in Humant T leukemia virus do?
It is a transcriptional activator of viral RNA and it works like an oncogene in cell culture by activating cellular genes and signal transduction
Discuss the Epidemiology of the Human T leukemia virus
it is endemic in sub-saharan africa, japan and the pacific, the caribean, south and central america
What is the Human T leukemia virus related to?
Simian T cell leukemia virus giving us the idea that it probably rose from a zoonotic event
What is a big complication with human T leukemia Virus?
Aggresive adult T cell leukemia
What are the characteristic of aggressive adult T-cell leukemia?
It will produce skin lesions which is why it is also call cutaneous T cell lymphoma. I also cause mild immunodeficiency without cancer
It can also cause chronic myelopathy or tropical spastic paraparesis which is an inflammatory disease
What cell does the human T leukemia virus infect
CD4+ T cells
Describe the diagnosis of the HTLV virus
You can use elisa for antibodies
-PCR of provirus of viral genome
Discuss the transmission of HTLV
This virus is highly cell associated so there is little virus found in fluids
primarily mother to child through breastfeeding
sexually
infected blood to blood products
sharing needles
What is the treatment for the HTLV
There is no vaccine but you can treat the cancer
Where can you get HTLV 2
From a T cell hairy Leukemia
What is HTLV-3 called now?
HIV-1
What is gene therapy
This is when you insert a functioning gene into cel with a certain dysfunction so that you can increase its cellular function
What is the gene inserted in gene therapy called?
A transgene
Why would you want to add a gene to a cell?
The absence of that gene in the cell causes disease and you want to fix it
- you can make the cell more sensitive to a drug to target disease
- you can make the immune system target the specific cell
- or you can induce cell proliferation for tissue repair
- you can even delete a gene
- increase p53 function
How do you add a gene to a cell?
Ex vivo (out of the body where you remove a cell from the body and put the gene into it, then insert the cell into the patient) In vivo (in the body where you inject a vector into the patient that will essentially put the gene into the person bu there are issues with targeting efficiency and the immune response)
What is a vector in terms of gene therapy?
In gene therapy this is an agent that transfers genetic material from one cell to another
What are the three types of vectors
Viral vector
Non-viral vector
combination vector
What is a viral vecto
A virus where the genome has been altered so that it codes for extra genes
What are the limitations to using a viral vector
It has tropism and immune recognition
What is a non-viral vector
This is not as efficient as using a virus vector, it has less immune recognition, it is expensive and it can be naked DNA
What is a combination vector?
This is trying to mix both the viral and non-viral vector but it is still under development
What are the two types of viral vectors?
Defective and replication competant vectors
What kind of viral vector is modified so that it cannot replicate on its own?
A defective vector
Describe a defective vector
Where the insertion of the new viral vector does not result in replication of its own.
This works like an acute transforming retrovirus
What are replication competent viral vectors?
Vector that are inserted in the genome, but it has the capabilities replicating on its own because there is enough in the viral genome to support replication
Why is a defective viral vector safer?
There is a fear that the replication competent viral vector will have the capability of producing viruses that will be able to revert and create a virus that will cause disease in the person
What viruses are used as a viral vector?
adenovirus retrovirus adeno-associated virus poxvirus herpesvirus
Why was there a failure in gene therapy in 1999
the immune response was so strong that it lead to organ failure
What caused the first success in gene therapy?
using a retrovirus ex vivo where the cells where then put back into the patient
What category of retrovirus is HIV in
complex retrovirus
In HIV what proteins are made by the gag complex?
MA-matrix
CA-capsid (p24)
NC-nucleocapsid
What does the HIV matrix protein do?
coats the inside of the envelope and helps the DNA get into the nucleus
What does the HIV capsid protein do?
It forms a shell around the genome
What does the HIV nucleocapsid protein do?
binds to genomic RNA
What proteins in HIV are part of the pol group of genes?
PR-protease
RT-reverse transcriptase
IN-integrase
-functions of these proteins are self explanitary
What proteins are part of the env complex of proteins
SU-surface protein (gp120)
TM-trans-membrane protein
What does the HIV SU protein do?
it binds to the receptors on the cell
What does the HIV TM protein do
trans-membrane protein and it mediates fusion of the virus
What does the vpr HIV protein do?
virion protein R and it facilitate nuclear entry of DNA before integration
What is HIV gp120
the surface protein
-stands for glycoprotein
what is HIV gp41
the protein that mediates fusion
-stands for glycoprotein
what are the function of the nonstructural protein in HIV
- There is a protein that inactivates host defenses
- there is a protein that promotes receptor degredation and inactivate the host defenses
- a protein that up regulates the transcription of HIV genes
- a protein that plays a role exportin the spliced and unspliced mRNA
- there is a protein that regulates MHC 1 and CD4
When the HIV viral genome is first transcribes what does it make
two mRNAs, on for gag-pol and one for Env
What is unique about the HIV virion?
it has a strange nucleocapsid shape, almost like a chip
Describe the pathogenesis of the HIV infection
first the virus will enter the mucosal surface but it does not infect the epithelial cells instead it will attach to the dendritic cells, but again it does not infect it. Then the dendritic cell will bring the virus to a CD4+ T cell in the lymph node where the virus will then replicate in the blood. The lymphatic tissue will then move thorugh out the bod and infect the lymphatic tissue. The biggest cell it infect are the GALT cells
Why does HIV mainly infect the GALT cells?
These are the gut associated lymphoid tissue and this is because there is a large abundance of CD4+ T cells
After HIV is cleared from the body by the immune system, where does the virus still replicate?
lymph nodes and GALT
What does the constant HIV replication in lymph nodes and GALT lead to?
The CD4+ T cells over time will degrade leading to a large spike in viruses and a huge increase in viral replication
What is the major cause of infection by HIV patients?
A depletion of the immune response due to the death of CD4+ T cells in lymph nodes and GALT cells
What are the two types of HIV-1
R5 tropic (M tropic) and X4 virus (T tropic) and this is based off of the co-receptor or the trans-membrane protein on the virion
What are the differences between X4 HIV virus and R5 Tropic HIV virus
The M tropic one is the transmitted virus and it can infect macrophages
Be able to draw the immune response to HIV graph
look at graph
Name the phases of the HIV infection
flu-like disease
asymptomatic phase
symptomatic phase
aids
What happens in the flu-like phase of HIV or primary infection
fever, swollen lymph nodes, flu-like symptoms
What happens in the asymptomatic phase of an HIV infection?
no disease
What happend in the symptomatic phase/AID of the HIV infection
immunosuppression that will ultimately lead to death in the patient
What usually determines how long it will take for HIV to become full blown AIDS?
how long it takes to clear the primary infection. This is known as the set point, and the shorter it is, that is how good your immune system
What is the set point in an HIV infection?
This is how high the viral lead is at the end of the asymptomatic phase. The higher, the faster the progression to AIDS
During an HIV infection discuss how the CTL corresponds to the progression of HIV to AIDS?
strong CTL (CD8+ T cell) response will cause a slower progression because it means you have a strong immune system -a weak CTL response with a strong antibody response means that you do not have enough cytotoxic T cells in your body causing a fast progression to AIDS
what kind of people have a faster progression to AIDS from HIV?
infants, transfusion recipients, hemophiliacs
What are the patterns of progression in HIV infections?
Fast progressors
slow progressors
long term non progressors
elite controllers
What does it mean to be a long term non progressor with an HIV infection
This means that you have a detectable virus but you do not have a decrease in the CD4+T cell count
What is an elite controller in an HIV infection?
A person who is infected but there is no virus in the plasma so the infection never proceeds to AIDS
What happens during the AIDS infection
the immune system is destroyed by AIDS because of the death of CD4+ T cells which will affect the CD8+ cells and B cells. This cause what would normally be a small disease in people an opotunistic infection
What is an opotunisitic infection
In AIDS patients, when the disease has been compromised so much,even a small infection will cause a large infection and cause the disease to go wild
What are the variations in HIV called?
Clades
What are the three major genetic lineages of HIV?
M (major)
O (outlier)
N (non-M, non-O)
the different variants in these are called sub types or clades
What virus is HIV related to?
Simian immunodeficiency virus in non-human primates showing that this probably came from zoonotic transmission
What is different in SIV in their hosts as compared to the HIV infection in humans?
the SIV virus is asymptomatic in their hosts, but when chimpanzees acquire this virus it is not symptomatic
What happens when a chimpanzee gets SIV from monkeys?
It will not be asymptomatic and the Chimpanzee will get AIDS
How is HIV spread in adults?
Sexual contact through genital secretions
injection drug use and unsteralized needles
contaminated blood through hospital procedures
-transplant of organs
-these transmission routes change throughout the world
How can you reduce transmission of HIV
Use condoms and male circumcision may decrease the risk, due to lower CD4+ cells
How is HIV transmitted to children?
in utero
through blood
genital secretions
breast milk
How can a mother decrease the risk of transferring HIV to her child when pregnant?
antiretroviral therapy
What is the problem with the vertical transmission of HIV?
the time it takes to become full blown aids is highly shortened
Discuss HIV diagnosis
Detection of anti-HIV antibodies by looking at blood using ELISA test
There is also a home rapid response test
What is hard about HIV diagnosis?
It takes about four to six weeks to get antibodies and sometimes it can take up to 6 months
When the HIV virus is diagnosed, what guide therapy is followed
quantitative PCR for viral load
CD4+T cell count
assay for drug resistance of virus
Where is HIV in greatest amount?
Sub-saharan africa
most prevalent in low and middle income famalies
What characteristic about HIV that makes finding an effective vaccine or treatment difficult?
The fact that it replicates and evolves at an enormous rate
due to the high mutation rate of HIV, what kind of species are created?
Quasi-species
Why do people nee long term drug treatment of HIV?
the infected cells harbor the latent virus and activation can occur slowly over the years
What is one of the most effective treatments for HIV
highly active antiretroviral therapy
HAART
What is HAART
Highly active antiretroviral therapy where it contains multiple types of HIV drugs. It includes two reverse transcriptases and an integrase inhibitor and a protease inhibitor
What is the problem with long term antiretrovial drug usage?
difficult to maintain constant pill habit
- cost
- a lot of side effects
What is Pre-exposure Prophylaxis?
This is when you use HAART before HIV exposure to reduce the risk from getting HIV at high risk
The drug is called truvida
What has gone wrong with giving babies HAART soon after birth in high risk mothers
there are many reports of the virus rebounding in the kids
What was the proposed vaccine for HIV?
Sanofi/Vaxgen
Describe the assumptions with Sanofi/vaxgen
It tried to insert some of the HIV genes into the canarypox virus
What was the outcome for the Sanofi/Vaxgen vaccine experiment
It was statistically significant in preventing HIV but it was not that impressive data
-It had no effect on CD4+ T cell count
Describe the HIV-2 virus in broad terms
found in west africa
much less common than HIV-1
-thought to arise from a different primate species
-usually more controllable
What is a strong indicator for HIV prognosis
Set point
What is the largest human Virus?
poxviridae
Describe the viral structure of the poxviridae
It is neither icosahedral nor is it helical, it is a shape of its own
What DNA virus replicates in the cytoplasm of the cell?
poxviridae therefore it must have its own RNA polymerase
What are the unique features of the poxviridae?
It replicates in the cytoplasm even though it is a DNA virus
- The ends of the DNA strand are connected to the complementary DNA, they are fused
- It has a different subset of capsid shape, looks like a brick
- It is the largest human virus
What poxviruses are obligate human pathogens?
Variola virus
mollusca contagiosum virus
What family is mollusca contagiosum in?
poxviridae
Describe the disease of mollusca contagiosum
It is very mild pox virus that causes a very mild skin disease with raised pink bumps on the skin
How is mollusca contagiosum spread?
From skin to skin contact (Wrestlers get this quite often)
-By scratching or picking the bump
How are immunosuppressed patients affected by molluscum contagiosum?
they usually just get larger growths
Where doe Molluscum Contagiosum occur?
All over the world
How is molluscum Contagiosum diagnosed?
Usually isn’t because it is so mild
What is the treatment for molluscum contagiosum?
Similar for the human papilloma virus, cryotherapy or sialicylic acid treatment, but it usually isn’t treated because it is so minor
How is the variola virus and molluscum contagiosum different in terms of scarring?
Molluscum contagiosum virus does not leave scars while the variolla virus does
What family and genus is the variola virus in?
Family: poxviridae
genus: Orthopoxvirus
What are the two major types of variola virus?
variola major (30% fatality) and variola minor (1-2% fatality)
Which variola virus major type is most fatal?
variola major
How was the variolla virus spread?
through inhalation of the virus in the respiratory tract
-it is very weakly spread as a fomite
What disease does the variolla virus cause?
Small pox
Describe the pathogenesis of the variolla virus
First the virus is inhaled and begins to replicate in the upper respiratory tract. The virus is the disseminated through viremia. The is then infected during secondary viremia. The pox will then rise all over the body, often leaving scars if the patient survives
Where is the variolla virus now?
small pox disease has been eradicated from the world, although two samples are stored in CDC and in Russia
Where does the vaccine for the variola virus come from?
the Vaccinia virus because the two viruses are homologous and they share a few of the same antigenic determinants
What is common in both the vaccinia virus and the variola virus?
antigenic determinants
What is are the proteins that antibodies are made to called?
antigenic determinants
What was the original method of vaccination called?
Variolation
How did the vaccinia virus come about?
when Jenner found out that you can treat cowpox by taking some of the lesions and giving it to people in order to illicit an immune response. They got the name from the word for cow
what was used to prevent the variola virus?
Vaccinia virus
What are the dangers with the vaccinia virus
one in a million people dies from complications with the vaccine
- The major side effects include large sores and heart problems
- people with eczema should not be given the virus because this can cause a life threatening pox all over the body
What is necessary for eradication of a virus?
No animal resivoir minimal serotypes that cause disease -no persistance -causes acute recognizable spread -You need the world to eliminate it which costs a lot of money
What made it possible for the eradication of smallpox?
- The vaccine worked for variola virus and it only has one major serotype making the vaccine simple
- the disease is also easily diagnosed based on the scars, and there is no long term persistance with the disease
- There is no animal host reservoir
- The disease was so bad that all of the world was willing to promote elimination
How is the monkey pox virus spread
from prairie dogs to humans (came from zoonotic origins
Describe the disease of monkey pox
it is a more mild form of small pox
- fever, headache, swollen lymph nodes
- rash
- the pox will crust over leading it to be cleared in about 2 to 4 weeks
- can be lethal
Where is monkey pox endemic?
Africa (fatality rates usually center around here
Why was there a rise in monkey pox?
we no longer use the vaccinations for small pox therefore there is no protection against monkey pox
Why is the variolla virus a fear in bioterror?
It is very easily disseminated to people. It causes high mortality rates and outbreak would cause major panic
What are the three classes for potential viral bioterror agents?
Class A: agents that provide the similar aspects of disease as the variola virus
Class B: Viral encephalitis (moderately easy to spread with moderate death rates)
Class C: Emerging viruses
