Exam I: Virology II

Question 1

Epstein Barr Virus (EBV) HHV-4

Answer 1

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

Question 2

EBV: Epidemiology

Answer 2

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

Question 3

EBV: Clinical Syndromes

Answer 3

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

Question 4

Cytomegalovirus (CMV; HHV-5): Pathogenesis and Epidemiology

Answer 4

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

Question 5

CMV Common Transmission

Answer 5

1. 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
2. Birth, milk to nursing babies: mild disease, heterophile negative mononucleosis
3. Sexually & blood transfusions: mild, heterophile negative mononucleosis
4. Reactivation in transplanted organ: transplant patients
   Interstitial pneumonitis and systemic disease
5. Reactivation in transplanted organ AIDS patient
   CMV retinitis, pneumonitis and systemic disease

Question 6

CMV Retinitis

Answer 6

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

Question 7

CMV Treatment

Answer 7

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

Question 8

Roseolovirus

Answer 8

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

Question 9

Hepadnaviridae

Answer 9

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

Question 10

HBV Replication

Answer 10

Intracellular mature virus (IMV): represents the majority of infectious progeny and remains inside the host cell
Extracellular enveloped virus (EEV)

Question 11

HBV Epidemiology

Answer 11

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)

Question 12

HBV: Clinical Symptoms

Answer 12

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

Question 13

HBV Treatment

Answer 13

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

Question 14

Smallpox

Answer 14

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

Question 15

Poxviruses: Morphology, Pathogenesis, and Transmission

Answer 15

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

Question 16

Smallpox: Clinical Syndromes

Answer 16

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

Question 17

Pox: Molluscum contagiosum & Orf

Answer 17

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

Question 18

Paramyxoviridae

Answer 18

Parainfluenza virus, measles, mumps, respiratory syncytial virus (RSV)
RNA virus family

Question 19

Orthomyxoviridae

Answer 19

Influenza virus types A, B, and C

RNA virus family

Question 20

Arenaviridae

Answer 20

Lassa fever virus, lymphocytic choriomeningitis virus

RNA virus family

Question 21

Rhabdoviridae

Answer 21

Rabies virus, vesicular stomatitis virus

RNA virus family

Question 22

Filoviridae

Answer 22

Ebola virus, Marburg virus

RNA virus family

Question 23

Bunyaviridae

Answer 23

California encephalitis virus, Hanta virus, hemorrhagic fever virus, Rift valley fever
RNA virus family

Question 24

Retroviridae

Answer 24

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

Question 25

Reoviridae

Answer 25

Rotavirus, Colorado tick fever virus | RNA virus family

Question 26

Picornaviridae

Answer 26

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

Question 27

Togaviridae

Answer 27

``` 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 ```

Question 28

Flaviviridae

Answer 28

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

Question 29

Caliciviridae

Answer 29

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%

Question 30

Coronavirus

Answer 30

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)

Question 31

RNA Virus Strategies

Answer 31

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: 1. Positive stranded RNA that acts like mRNA: no RNA dependent RNA polymerase, initially undergoes translation, and RNA alone is infective 2. Negative stranded RNA and dsRNA: contains a RNA dependent RNA polymerase, initially undergoes transcription, and RNA alone is not infective

Question 32

RNA to mRNA

Answer 32

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

Question 33

Dengue Fever/Break Bone Fever: General Information

Answer 33

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

Question 34

Yellow Fever

Answer 34

``` Flavivirus causes hemorrhagic fever and hepatitis Vector: mosquito Hosts: primates and humans Distribution: Africa and South America ```

Question 35

St. Louis Encephalitis (SLE)

Answer 35

``` Flavivirus causes encephalitis Vector: mosquito Host: birds Distribution: Americas ```

Question 36

Japanese Encephalitis (JE)

Answer 36

``` Flavivirus causes encephalitis Vector: mosquito Hosts: pigs and birds Distribution: India, China, Japan, SE Asia ```

Question 37

West Nile (WN)

Answer 37

``` Flavivirus causes febrile illness Vector: mosquito Host: birds Distribution: Africa, Middle East, and Europe ```

Question 38

Flavivirus: Epidemiology

Answer 38

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

Question 39

Dengue Fever/Break Bone Fever: Manifestation

Answer 39

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)

Question 40

Dengue Fever/Break Bone Fever: Clinical Symptoms

Answer 40

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

Question 41

St. Louis Encephalitis

Answer 41

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

Question 42

Yellow Fever

Answer 42

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)

Question 43

West Nile Virus

Answer 43

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

Question 44

Dead Host: West Nile Virus

Answer 44

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

Question 45

Hepatitis C (HCV)

Answer 45

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

Question 46

Hepatitis C (HCV): Transmission

Answer 46

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) ```

Question 47

Picornavirus: Enterovirus, Rhinovirus, and Hepatovirus

Answer 47

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

Question 48

Picornaviridae: General Information

Answer 48

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

Question 49

Picornaviridae: Mechanism of Infection

Answer 49

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

Question 50

Picorniviridae: Pathogenesis

Answer 50

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)

Question 51

Picorniviridae: Epidemiology

Answer 51

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

Question 52

Enterovirus Pathogensis

Answer 52

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

Question 53

Poliomyelitis/ Polio/ Infantile paralysis

Answer 53

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

Question 54

Coxsackie Virus A

Answer 54

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)

Question 55

Coxsackie Virus B

Answer 55

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

Question 56

Hepatitis A Virus

Answer 56

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

Question 57

Rhinoviruses

Answer 57

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

Question 58

Picornaviridae Treatment and Prevention

Answer 58

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