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