HIV, Hepatitis, Herpes

Slackers Facts by Mike Ori

Disclaimer

The information represents my understanding only so errors and omissions are probably rampant. It has not been vetted or reviewed by faculty. The source is our class notes.

The document can mostly be used forward and backward. I tried to mark questionable stuff with (?).

If you want it to look pretty, steal some crayons and go to town.

Finally…

If you’re a gunner, buck up and do your own work.

What are the retrovirus groups

OncoretrovirusLentivirus

What are the members of each retroviral group?

Oncoretrovirus – HTLV I/IILentivirus – HIV I/II

Describe retrovirus morphology

Encapsulated icosahedral ssRNA (+) diploid

What do the name prefixes tell you?

Onco = tumorLenti = slow

What is the target tissue for retroviruses

T cells

What tumors are associated with HTLV

HTLV I – Adult T-cell leukemiasHTLV II – Hairy cell leukemias

What are the three most important retroviral proteins?

Reverse transcriptaseIntegraseprotease

Describe retroviral promoters

Consist of long terminal repeats that are situated upstream of viral genes

What are the products of the gag gene

Structural genes for matrix, capsid, nucleocapsid

What is the function of the pol genes

DNA synthesis and maintenance and protein activation.

Protease, reverse transcriptase, integrase

What is the function of the env genes

Surface glycoproteins and transmembrane proteins

GP120 and GP41

What does HIV rev do?

Transports mRNA from the nucleus

What does HIV tat do

Promotes the transcription of HIV genes by interacting with LTR.

What are the analogous HTLV genes for tat and rev?

Tax and rex

What is the basis for HTLV oncogenesis?

Tax interacts with host cell promoter sequences that induce oncogenesis.

Is HIV oncogenic

No, HIV tat protein is more specific and does not interact with host cell promoters.

What the general mechanisms of oncogenesis

Expression of viral genes that interfere with or cause over-expression of host proteins that

lead to defective cell cycle maintenance.Insertional mutagenesis - Insertion of viral genome into the host genome in a way that

causes dysregulation.Acute transforming viruses – incorporate a host

oncogene in the viral genome.

What are the primary HIV surface glycoproteins and what are their functions?

GP120 – interacts with host cell receptorsGP41 – initiates fusion of viral and host

membranes

What are CCR5 and CXCR4

These are coreceptor molecules on the surface of some human cells whose binding is required in addition to GP120-->CD4

Where are CCR5 and CXCR-4 found

CCR5 is found in dendritic cells and macrophages in the periphery. CXCR-4 is

found on CD4 T-lymphocytes

Where is the highest concentration of HIV virus found

In lymph nodes

Describe why antibodies are less effective against HIV

HIV infects adjacent cells during the budding process. It is not exposed to antibodies. Note

that HIV proteins on the plasma membrane are targets for antibodies though.

How does HIV reduce its exposure to cytotoxic T-cells

It down-regulates MHC-I and MHC-II

Which is more infective for sexual transmission CCR5 or CXCR-4?

CCR5. It is found on dendritic cells and macrophages

List the hepatitis viruses

A, B, C, D, E, GWhere is F?

List the routes of transmission for each

A,E – entericB,D – Sex, blood, and rock and roll

C – BloodG – Enteric?

Which viruses are associated with hepatitis

EBVCMVVZV

Yellow fever

What family does hep A belong to?

Picornaviridae

How do people come into contact with HAV

Transmission is ultimately fecal oralPerson to person

ShellfishWater

What are the words to the hepatitis song aired on Phoenix TV in the late 70’s?

Hepatitis has some symptoms we should learn to recognizeLike fever, feeling very tired and loss of appetite.

Your stomach hurts, you feel real sick, you will not eat a bite.Your eyes sometimes look yellow when they only should be white.

Wash your hands after going to the bathroomWash your hands after changing baby too'Cause we don't want to spread hepatitis

And we don't want hepatitis to catch you. Who? YOU!

What is the diagnostic test for HAV

IgM titer

What is the incubation period for HAV?

14-40d

Describe the structure of hepatitis B

Smallest DNA virus. Partial double strand circular genome. Enveloped virus

Why does Hep B have a reverse transcriptase

Hep B uses RT during the viral replication process to convert whole genome RNA

transcripts into DNA.

Where does reverse transcription occur for hep B?

In the nascent virus particle.

Why is the second strand often incomplete?

There are insufficient nucleotides enclosed in the viral envelope to complete the strand

Why are RT inhibitors relatively ineffective against HBV?

Penetration of the viral coat in sufficient concentration is a barrier to their efficacy.

What is the epidemiology of HBV?

0.1 to 0.5% chronic carriers. 50% of infections are related to sexual activity.

What % of infected people become chronic carriers?

10-20%

What are the long term sequelae of chronic HBV infection?

CirrhosisHepatocellular carcinoma (200x increase)

What is the incubation period for HBV?

160 days

What antibodies may be elaborated in response to HBV?

Anti coreAnti surface

Anti E

Which antibody is considered protective?

Anti surface (anti HBsAg)

Which Ab is the first to be produced

Anti core

Which Ab is next

Anti E

Which antibody is last to be produced

Anti surface

What is the basis for inoculating infants against HBV at birth

The incubation period for HBV is very long. Hence, an early inoculation can prevent HBV

infection from establishing even if the neonate is infected during parturition.

For what other virus is post exposure vaccination used?

Rabies virus

What is the tx for HBV?

IFN-alpha

What family does Hepatitis B virus belong to?

Hepadenaviridae

What family does hepatitis C belong to

Flaviviridae

What are the other members of flaviviridae?

Yellow fever, dengue, St Louis, west nile

What is the chronicity for HCV?

85%

What is the primary mode of transmission of HCV?

Needle sharing

What are the sequelae to HCV?

CirrhosisHepatocellular carcinoma

What is the structure of HCV?

Enveloped ssRNA (+)

What is unusual about the chronicity of HCV?

Chronic viruses need to have a method of genome persistence. RNA viruses (HCV=RNA) are generally considered too fragile to persist

within cells (replicate or die) but HCV is able to do so through unknown mechanisms.

What accounts for the damage to liver parenchyma?

The immune response is probably the major culprit causing damage.

What is the tx for HCV?

IFN-alpha +/- ribavirin

What family does hepatitis D virus belong to?

It is unclassified

What is the epidemiology of HBV?

Pretty much the same as HBV. Sex and blood.

What is unique about the relationship of HBV and HDV?

HDV requires HBV as HDV’s genome does not encode surface antigen. Thus it is impossible to be infected with HDV unless HBV infection

is present.

Describe the hepatitis that occurs with HBV/HDV coninfection

Fulminant hepatitis. Often presents as an acute exacerbation in a chronic HBV patient.

What is the diagnostic test for HDV?

Anti-Delta antigen antibody titer

Describe the difference between HAV and HEV

HEV is an unclassified virus similar to calcivirus (ssRNA (+) icosahedral). It is typically only an issue in pregnant women where it can cause fulminant hepititis. Typically found on indian

subcontinent.

Why am I not describing Hepatitis G

Because while it is found in 2% of blood donors, it is not yet linked to disease.

To which family do herpes viruses belong

Please that’s easy…Herpesviridae

What is the morphology of herpesvirus

Large enveloped linear dsDNA icosahedral and enveloped virus

List the herpes viruses

HSV-1HSV-2

Varicella-zoster (VZV)Cytomegalovirus

Epstein-barrHHV-6HHV-7HHV-8

What are the general rules for HSV 1 and 2

HSV 1 is above the waist, HSV 2 is below. These are loose rules though as cross infection is

known.

What is the tropic tissue for HSV 1/2

Skin where it causes ulcerating lesions

Why do people have recurring lesions with HSV 1/2

HSV invades the trigeminal (1) or sacral (2) nerve ganglions. It periodically reactivates and then

flows down the axons to replicate in the epithelial cells.

What are the theories for HSV reactivation

1. Stress and other factors cause the latent virus to begin replicating in the ganglion. The

resulting virions are shed from the axon tip and then begin replication in the epithelium.

2. A low level of virus production occurs within ganglion cells and is release in a burst from

the axon. These then replicate in the epithelium. (store and release)

What are the gene classes in HSV. What are their functions?

Alpha – immediate early, regulatoryBeta – early, genome replication

Gamma – Late, structural

What is the role of the LAT1 gene in maintianing HSV latency.

LAT1 transcripts are antisense to alpha-0. This blocks the action of alpha-0.

Thus neither can live while the other survives.

Where does HSV assembly occur

In the nucleus

Where does HSV bud from

The nucleus into the ER

On what cellular membrane are HAV’s spikes found?

The inner membrane of the ER.

How is HSV released from the cell

By exocytosis

What form a blindness does HSV cause

Keratoconjunctivitis leading to corneal ulceration

What is the form of the HSV genome during latency

It is a circular extrachomasomal element

Which drug is used for TX of HSV?

AcyclovirFoscarnet if resistant

What is the time course for VZV initial infection

Incubation for 14 daysRecovery in 2 weeks

What is shingles

Reactivation of VZV in older patients.

Describe the VZV vaccine

Live attenuated

Describe CMV clinical disease

Normally no sx except in immunocompromised where it can have sx of pneumonia.

Can cause mono.

Describe the cytology of CMV infection

Nuclear and cytoplasmic inclusion bodies with owl’s eye appearance. Giant cell formation.

Describe congenital CMV sequelae

Blueberry muffin babiesHearing loss, retardation, hepatosplenomegally

What is the most common EBV disease

Infectious mononucleosis

Distinguish EBV and CMV mono

EBV is mono-spot positiveCMV is mono-spot negative

What is the basis of the mono-spot test

EBV elicits heterophile antibodies against sheep RBC.

What long term sequelae is EBV associated with

Burkitt’s lymphoma in africa and nasopharyngeal carcinoma in asia

What disease is caused by HHV-6?

Roseola infantumMany other agents cause as well

What disease is associated with HHV-8

Kaposi’s sarcoma