Exam I: Virology II Flashcards
Epstein Barr Virus (EBV) HHV-4
EBV enter B cell by binding complement receptor CR2 (CD21)
Pathogenesis:
Infects B cells and epithelial cells of oropharynx
Lead to viral shedding in saliva, which is contagious
Virus spread to blood, lymph
EBV stimulate B cell mitosis leading to increased number of B cells that harbor EBV in their genome
2 kinds of disease may result:
Overactive immune response to EBV= mononucleosis
Weak immune response= Burkitt lymphoma
EBV: Epidemiology
More than 90% of infected shed virus in saliva asymptomatically for life
Kissing as means of transmission
Disease is usually sub-clinical in children
70% of population infected by 30 years
Many, in US, get it in 1st year of college
EBV: Clinical Syndromes
Mononucleosis: high fever, malaise, pharyngitis, lymphadenopathy, hepatosplenomegaly, fatigue, headache
Hairy leukoplakia: consists of white vertical folds or ridges along the lateral borders of the tongue
Oncogenic: Burkitt lymphoma, nasopharyngeal carcinoma, lymphoma
Cytomegalovirus (CMV; HHV-5): Pathogenesis and Epidemiology
Pathogenesis: Persistent, latent infections Infect mononuclear cells, kidney, heart Replicate in ductal epithelial cells which promotes the excretion of virus in most bodily fluids Less common/less disease
Epidemiology:
Virus can be found in urine, blood, saliva, tears, breast milk, semen, stool, amniotic fluid, vaginal and cervical secretions
Can be spread: orally, sexually, congenital in utero, with blood and organ transplants
HIV infected patients at risk
CMV Common Transmission
- In utero: most common in utero infection
Disease ranges from infected with no defects to cytomegalic inclusion disease: jaundice, hepatosplenomegaly, thrombocytopenic purpura, pneumonitis and CNS damage to death - Birth, milk to nursing babies: mild disease, heterophile negative mononucleosis
- Sexually & blood transfusions: mild, heterophile negative mononucleosis
- Reactivation in transplanted organ: transplant patients
Interstitial pneumonitis and systemic disease - Reactivation in transplanted organ AIDS patient
CMV retinitis, pneumonitis and systemic disease
CMV Retinitis
Cytomegalovirus Retinitis is the most common opportunistic infection in HIV- usually seen when CD4+T<50
Prior to highly active anti-retroviral therapy, CMV retinitis was easily recognized as a “pizza pie” retinopathy
Patients on HAART (Highly Active Antiretroviral Therapy), may be more difficult to diagnose
Retinal detachment frequently complicates CMV retinitis
CMV Treatment
Ganciclovir: synthetic analogue of 2’-deoxy-guanosine
It is first phosphorylated to a dGTP analogue
dGTP analogue inhibits the incorporation of dGTP by viral DNA polymerase
Result: termination of elongation of viral DNA
Give to AIDS patients to make the disease less severe
Foscarnet (Foscavir): is classic inhibitor of herpesviruses
Foscarnet is, a phosphonic acid, a structural mimic of the anion pyrophosphate that selectively inhibits the pyrophosphate binding site on viral DNA polymerases
Because foscarnet is not activated by thymidine kinase (tk), it maintains activity in tk–viruses and gained resistance to acyclovir or ganciclovir
Foscarnet is used in acyclovir- or ganciclovir-resistant disease
Roseolovirus
A genus of the family HERPESVIRIDAE
Subfamily BETAHERPESVIRINAE
Viruses have been isolated from lymphocytes
HUMAN HERPESVIRUS 6 (HHV6) is the type species
6th disease –rash
Exanthem subitum, Roseola infantum
Cause: HHV6-B or HHV7
Hepadnaviridae
Hepatitis B virus (HBV): small, enveloped DNA virus,
partially DS -use a reverse transcriptase and RNA intermediate during replication
B hepatitis: acute, chronic, asymptomatic or symptomatic depending on the person’s immune response to the virus
Virus begins to replicate in the hepatocytes within 3 days of infection where no harm done at first
Symptoms may not appear until 6-7 weeks or later
Copies of HBV genome are integrated into hepatocytes = latency
From the liver to viremia (blood) then spread to saliva, semen, vaginal secretions and mother’s milk
All these fluids are contagious
HBV Replication
Intracellular mature virus (IMV): represents the majority of infectious progeny and remains inside the host cell
Extracellular enveloped virus (EEV)
HBV Epidemiology
More than 300,000 cases/year with 4,000 deaths in the US Asymptomatic chronic carriers are a reservoir that keep spreading the disease Spread by: sexual contact, blood transfusion and exchange via sharing needles, acupuncture, ear piercing and tattooing Perinatal transmission (vertical transmission)
HBV: Clinical Symptoms
Acute infection:
Long incubation, insidious onset
Prodrome: fever, malaise, fatigue, anorexia, nausea & vomiting and abdominal pain
Icteric/jaundice stage- Bilirubin, the yellow breakdown product of normal heme catabolism is responsible for
Jaundice, yellowing of skin and eye-white, dark urine, pale stools, fulminant disease
1% may progress causing severe liver damage, cirrhosis and bleeding
Chronic infection: 5-10% with HBV
Usually after mild or apparent clinical symptoms
May only be detected by increased liver enzymes
10% with chronic HBV develop cirrhosis and liver failure
Primary hepatocellular carcinoma: major complication attributed to HBV in more than 80% of cases
HBV Treatment
No specific treatment
IFN-alpha for chronic disease
HBV Ig: for newborns and recently exposed patients
Drugs target: polymerase, reverse transcriptase
Lamivudine and anti-herpes drug famciclovir
Vaccine: HBsAG= hepatitis B surface antigen
Subunit vaccine 3 times
Smallpox
The Pharaoh Ramses V died of smallpox in 1157 B.C.
The disease reached Europe in 710 A.D.
It was transferred to America by Hernando Cortez in 1520
3.5 million Aztecs died in the next 2 years.
In the cities of 18th century Europe, smallpox reached plague proportions and was a feared scourge - highly infectious.
Five reigning European monarchs died from smallpox during the 18th century
Poxviruses: Morphology, Pathogenesis, and Transmission
Morphology: virions enveloped, composed of an external coat containing lipid and tubular or globular protein structures
Nucleocapsid brick-shaped to ovoid
Core usually biconcave with two lateral bodies
Largest, most complex virus, linear ds DNA genome
Replication in cytoplasm
Pathogenesis: virus enters the upper respiratory tract by inhalation and disseminates in lymphatics → viremia
After a secondary viremia, the virus infects all dermal tissues and internal organs leading to the classic “pocks” formation
Transmission: acquired via respiratory route and close contact
Smallpox: Clinical Syndromes
Variola major: virus replicates in respiratory tract, travels to lymph glands, then to blood (viremia)
Incubation of 5-17 days
15-40% mortality rate
Variola minor
1% mortality rate
No treatment
Vaccine available but no longer produced in large quantities because disease is eradicated
Encephalitis is an important complication
Pox: Molluscum contagiosum & Orf
Molluscum contagiosum: a minor infectious warty papule of the skin with a central umbilication (depression)
transferred by direct contact, sometimes as a venereal disease
ORF – a worldwide occupational disease associated with handling sheep and goats afflicted with “scabby mouth”.
In humans it manifests as a single painless, papulo-vesicular lesion on the hand, forearm or face
PAINLESS
Paramyxoviridae
Parainfluenza virus, measles, mumps, respiratory syncytial virus (RSV)
RNA virus family
Orthomyxoviridae
Influenza virus types A, B, and C
RNA virus family
Arenaviridae
Lassa fever virus, lymphocytic choriomeningitis virus
RNA virus family
Rhabdoviridae
Rabies virus, vesicular stomatitis virus
RNA virus family
Filoviridae
Ebola virus, Marburg virus
RNA virus family
Bunyaviridae
California encephalitis virus, Hanta virus, hemorrhagic fever virus, Rift valley fever
RNA virus family
Retroviridae
HIV, human T cell leukemia virus, sarcoma
positive sense RNA
2 ss mRNA (diploid), has polymerase and RT
enveloped, pleomorphic (closed tube sphere, conical)
replication in the nucleus
RNA virus family
Reoviridae
Rotavirus, Colorado tick fever virus
RNA virus family
Picornaviridae
Rhinovirus, poliovirus, echoviruses, coxsackie virus, enterovirus, Hep A
linear ss mRNA, non segmented
no polymerase, naked, icosahedral
replication in the cytoplasm because positive sense RNA
RNA virus family
Togaviridae
Rubella virus, equine encephalitis viruses (eastern, western, and Venezuelan) Ross River virus linear ss mRNA, non segmented positive sense RNA no polymerase, enveloped shape: pleomorphic to sphere replication in the cytoplasm RNA virus family
Flaviviridae
Yellow fever virus, dengue virus, St. Louis encephalitis (SLE), West Nile encephalitis, Hep C
linear ss mRNA, non segmented, positive sense RNA
no polymerase, enveloped, spherical/icosahedral, replication in cytoplasm, RNA virus family
Vectors: mosquitoes, ticks, fleas
Replication: Genomic RNA is capped, not polyadenylated, and serves as mRNA for all proteins; the positive strand will be transcribed to a negative strand which will serve as the template to produce the original
Complementary RNA: antisense RNA, made from genomic RNA , serves as a template for progeny genomic RNA
Caliciviridae
Norwalk virus and Hep E; RNA virus family
positive sense RNA, linear ss mRNA, non segmented
no polymerase, naked, icosahedral, replication in the cytoplasm
Norwalk virus: naked icosahedral
Epidemic viral gastroenteritis with vomiting and diarrhea
Fecal-oral route and respiratory transmission possible
Immunocompromized may need to be hospitalized for rehydration therapy
Hepatitis E: fecal-oral route, mild, and low risk of mortality 1-2%, but mortality risk is higher in pregnant women- up to 20%
Coronavirus
Corona
positive sense RNA, linear ss mRNA, non segmented
no polymerase, enveloped, helical, replication in the cytoplasm, pleomorphic (adapt size/shape)
ss + RNA acts as mRNA
Large surface glycoprotein spikes give a crown appearance
Transmission by respiratory droplets
Second most common cause of the common cold
Peak in winter and early spring
SARS (severe acute respiratory syndrome)
RNA Virus Strategies
RNA to RNA requires RNA-dependent RNA polymerase (transcriptase)
RNA to DNA requires RNA-dependent DNA polymerase (Reverse transcriptase)
Host cell DNA to mRNA requiresDNA-dependent RNA polymerase
RNA without the DNA phase:
- Positive stranded RNA that acts like mRNA: no RNA dependent RNA polymerase, initially undergoes translation, and RNA alone is infective
- Negative stranded RNA and dsRNA: contains a RNA dependent RNA polymerase, initially undergoes transcription, and RNA alone is not infective
RNA to mRNA
Virus with negative sense RNA genome need to make mRNA first then a protein
RNA dependent RNA polymerase (RdRpase) is required for viral replication
RdRpase must be provided by the virus
Dengue Fever/Break Bone Fever: General Information
Flavivirus
causes febrile illness (uncertain cause), rash, hemorrhagic fever, and shock syndrome
Vector: mosquito
Host: humans
Distribution: worldwide, tropics; geographical spread is similar to malaria
Dengue is often found in urban areas of tropical nations, including Singapore, Taiwan, Indonesia, Philippines, India, and Brazil
1 million cases of Dengue fever and 250,000 cases of hemorrhagic fever /year
Vector: Aedes (A. aegypti) mosquito DAY FEEDER
Yellow Fever
Flavivirus causes hemorrhagic fever and hepatitis Vector: mosquito Hosts: primates and humans Distribution: Africa and South America
St. Louis Encephalitis (SLE)
Flavivirus causes encephalitis Vector: mosquito Host: birds Distribution: Americas
Japanese Encephalitis (JE)
Flavivirus causes encephalitis Vector: mosquito Hosts: pigs and birds Distribution: India, China, Japan, SE Asia
West Nile (WN)
Flavivirus causes febrile illness Vector: mosquito Host: birds Distribution: Africa, Middle East, and Europe
Flavivirus: Epidemiology
Arboviruses (Arthropod borne virus)
Infect vertebrate, invertebrate, arthropods, hosts
Initiate productive infection of the salivary gland in arthropod
Mosquito can transfer the disease from human to human, and the most common vector
Reservoir: birds and small mammals
Occur in wet summer and rainy season when mosquitoes breed
Starts as prodrome viremia/mild asymptomatic, then mild systemic disease affecting the vascular endothelium, macrophages, liver, spleen, and lymph nodes, then Ab block occurs to elicit severe disease that affects the brain (encephalitis strains), hemorrhagic fever/dengue fever, and hepatitis/yellow fever
Dengue Fever/Break Bone Fever: Manifestation
Sudden onset of fever, severe headache, muscle and joint pains rashes
The dengue rash is characteristically bright red petechiae that usually appears first on the lower limbs and the chest
There may also be gastritis with associated abdominal pain, nausea, vomiting or diarrhea
Other symptoms include: fever, bladder problems, constant headaches, severe dizziness, loss of appetite, red eyes (may be due to another cause)
Dengue Fever/Break Bone Fever: Clinical Symptoms
Some cases develop much milder symptoms, and can be misdiagnosed as influenza or other viral infection Thus travelers from tropical areas may inadvertently pass on dengue in their home countries, having not been properly diagnosed at the height of their illness
Flavivirus
Patients with dengue can pass on the infection
only through mosquitoes, blood products, while they are still febrile
The classic dengue fever lasts about six to seven days,
“Biphasic pattern”: refers to a smaller peak of fever at the trailing end of the disease
Cases of DHF show: higher fever, hemorrhagic phenomena, thrombocytopenia, hemoconcentration, cases of DSS has a high mortality rate
St. Louis Encephalitis
Flavivirus in North America
Vector: Culex mosquito
Occur primarily in the late summer or early fall
Range of disease: mild illness with fever and headache
more severe, headache, high fever, neck stiffness, stupor, disorientation, coma, tremors, occasional convulsions and spastic paralysis
Fatality ranges from 3-30%, aged people are more likely to have a fatal infection.
Aseptic meningitis: cannot see change in CSF
Severe overwhelming encephalitis
Large proportion of survivors end up with permanent neurologic damage
Dead end host: once a human has been infected with the virus it is not transmissible from that individual to other humans
Yellow Fever
Flavivirus
Severe systemic disease with degeneration of the liver, kidney, heart and hemorrhage
The liver involvement causes jaundice (yellow fever)
Massive gastrointestinal hemorrhages (black vomit)
Mortality rate approaches 50% (like ebola)
Symptoms: sudden onset of fever, backache with generalized muscle pain, nausea and vomiting, prostration (exhaustion), chills, headache, melena (black tarry stool)
West Nile Virus
Mosquito borne
Usually mild to asymptomatic disease; sometimes people will ignore the mild symptoms because it can indicate anything (cold, fle, etc.) unless they have the rash, then they seek attention
20% will have West Nile Fever: fever, headache, body aches, occasionally a rash on the trunk, swollen lymph nodes that lasts several days
West Nile Encephalitis is the severe form: high fever, neck stiffness, stupor, disorientation, coma, tremors, convulsions, muscle weakness and paralysis
1/150 persons will contract more severe form
Lasts several weeks
Incubation period is 3-14 days
Dead Host: West Nile Virus
The horse and the human are dead end hosts for some diseases like West Nile Virus
Infects humans by mosquito and the horse can be infected the same way, but they cannot reinfect the mosquito
Birds are important to the life cycle: 1. bird can reinfect the mosquito, so the disease is maintained between the two, but 2. the crow can maintain within the species- they infect each other without the mosquito—difficult for the eradication of the diseases
If the mosquito is eradicated, maybe calm it down
Hepatitis C (HCV)
Flaviviridae/Hepacvirus
Positive stranded RNA, enveloped
Hepatitis C virus is spread by blood-to-blood contact, sexual contact, NOT Arbovirus/No mosquito
The infection can cause asymptomatic liver inflammation
Chronic hepatitis can result in cirrhosis, fibrotic scarring of the liver, and liver cancer
Treatment: IFN-alpha, Ribavirin
Immunity: No vaccine, but passive, prophylactic Ig if suspect exposure before the onset of infection
Hepatitis C (HCV): Transmission
Blood products like transfusions & organ transplantation
Iatrogenic medical or dental exposure
Occupational exposure to blood like medical and dental personnel, first responders
Recreational exposure to blood like contact sports and slam dancing/moshing
Injection drug use and drug use by nasal inhalation (Drugs that are "snorted") Sexual contact Shared personal care items Body piercing and tattoos Vertical transmission (mother to fetus)
Picornavirus: Enterovirus, Rhinovirus, and Hepatovirus
Enterovirus: all enteroviruses and poliovirus; all are pico RNA viruses, rhinoviruses, and hepatoviruses (hepA virus is important)
Rhinovirus: human rhinovirus A and B
Hepatovirus: Hep A and Avian encephalomyelitis-like viruses
Picornaviridae: General Information
Positive ssRNA viruses, non-enveloped
Icosahedral capsid: enterovirus (echoviruses, polio virus, coxsackie A, coxsackie B), rhinovirus, hepatovirus (hepatitis A)
Cardiovirus, aphthovirus, parechovirus, erbovirus, kobuvirus, teschovirus
Picornaviridae: Mechanism of Infection
Viral replication: binds to cell surface receptors, conformational change in the viral capsid proteins, and myristic acids, RNA is injected inside the cell, RNA un-coats
(+) strand RNA genome is replicated through a double-stranded RNA intermediate that is formed using viral RDRP (RNA-dependent RNA polymerase) in the cytoplasm
The viral life cycle is very rapid, at 4-6 hours the virus particles assemble, and can sometimes be seen in the cytoplasm
At 8 hours the cell lyses to release the viral particles
Picorniviridae: Pathogenesis
Primary viremia: spreads virus to receptor bearing target cells where second phase of symptoms may occur
Secondary viremia
Polio: must cross blood brain barrier or access to brain by nerves innervating skeletal muscle
Viral production and shedding of enteroviruses from GI tract with feces
Virus stability: stable in stomach acid, in bile, in presence of proteases
Replicate at 37° C, considered high temp (body temp)
Picorniviridae: Epidemiology
Poliovirus, Coxsackie virus, Echovirus
Infection can be usually asymptomatic but can cause
cold-like symptoms or as severe as paralysis
These viruses do not cause enteric disease
Transmission fecal-oral
Portals of entry: upper respiratory tract, oropharynx, intestinal tract
Enterovirus Pathogensis
Entry via aerosols or ingestion, replication in oropharynx/tonsils or Peyer’s patches, virus in feces
Primary viremia leads to secondary viremia:
Coxsackie virus A and Echovirus = goes to skin causing hand, foot, and mouth disease and rash herpangina
Coxsackie virus B and Echovirus = goes to muscle causing myocarditis, pericarditis, and pleurodynia
Hep A = goes to liver
Echovirus and Polio =goes to meninges to cause meningitis
Polio = goes to the brain to cause paralysis/encephalitis
Poliomyelitis/ Polio/ Infantile paralysis
Poliomyelitis is an acute viral infectious disease
Spread from person to person primarily via the fecal-oral route
90% of polio infections have no symptoms at all
Viremia = exhibition of a range of symptoms
In fewer than 1% of cases the virus enters the CNS preferentially infecting and destroying motor neurons causing muscle weakness and acute flaccid paralysis
Different types of paralysis may occur, depending on the nerves involved
Spinal polio is the most common form, characterized by asymmetric paralysis that most often involves the legs.
Bulbar polio leads to weakness of muscles innervated by cranial nerves.
Bulbospinal polio is a combination of bulbar and spinal paralysis
Vaccines:
Sabin: Live attenuated, oral, best, GI immunity
Salk: injectable killed
Coxsackie Virus A
Herpangina: vesicles on soft palate and fauces (back of mouth to pharynx)
Hand, foot and mouth disease: an exanthema (rash) caused by Coxsackie type A16.
Symptoms include fever and blisters on the hands, palate and feet, but it subsides in a few days
Can cause: myocarditis, pericarditis, and aseptic meningitis (doesn’t show up in CSF testing)
Coxsackie Virus B
Aseptic meningitis, myositis, myocarditis, pericarditis
Myocarditis Bornholm disease (Pleurodynia, the Devil’s Grip), which is an upper respiratory tract infection can result in fever and sudden sharp pains in the intercostal muscles on one side of the chest, abdomen pain and vomiting
incubation period is 2 to 4 days
symptoms subside after a few days, butrelapses can occur
Hepatitis A Virus
Infectious hepatitis
Transmitted via the oral-fecal route, close contact, day-care centers, sexual contact, contaminated food
consumption of raw or undercooked shellfish from sewage infested water
Accounts for 40-50% of all hepatitis cases
Orally ingested virus enters the bloodstream via the lining of the intestinal tract then migrates to the liver parenchymal cells and these cells become infected because they have the immunoglobulin-like HAV cellular receptor on their surfaces
The virus replicates slowly, shed into the bile, and passed in the stool
There is only one HAV serotype worldwide humans are the only reservoir
The symptoms of HAV and HBV are very similar
The most obvious symptom is jaundice, but also abdominal pain, nausea, diarrhea, fatigue, and fever
No chronic infections with HAV, but some patients may experience symptoms for up to 9 months
Immunity: inactivated vaccine, active immunization
Hyperimmune serum for post exposure prophylaxis, which is passive immunity
Rhinoviruses
Human Rhinovirus and its Interaction with ICAM-1: the arrangement of the four viral proteins on the rhinovirus protein capsid creates canyons. The outer end of the ICAM-1 reaches into the canyons and binds with side chains located on the canyon floors.
Upper respiratory tract infection; common cold
Self limiting, and does not cause severe disease
Virus bind to ICAM receptor: Zn2+ compete with LFA-1 for ICAM-1 receptor sites reducing LFA-1 binding and suppressing inflammation
Virus: labile in acid and replicates at a lower temperature (33° C) so thrives in nasal passages
Picornaviridae Treatment and Prevention
Pleconaril: binds to a hydrophobic pocket in VP1 of picornaviruses; in enteroviruses, this prevents the virus from exposing its RNA, but in rhinoviruses it also prevents the virus attachment to host cell
Methylisoxazole compounds: stabilizes picornaviruses; coated virus remains in cytoplasm; 3-methylisoxazole group inserts in capsid VP1 and covers ion channel
Vaccines
IPV- inactivated (Salk) polio vaxine; injected
OPV- oral (Sabin, live attenuated) polio vaxine; most important; used worldwide
HAV- hepatitis A vaccine
