Module 7

How does the virus mature after budding?

protease cleaves the polyproteins

What is the

1) bind to cell recepter, enters through fusion (most) and releases NA in subviral structure 2) RT converts RNA to DNA 3) integration of DNA into host genome by integrase 4) genes transcribed by host DNA polymerase

What 2 characteristic features does retroviral integration result in?

1) some bases at the ends of LTRs are lost from viral DNA (allows cleavage from free hydroxls) 2) duplication of host DNA at insertion site

How long does the chronic stage last?

2-10 years, but continues to degrade the immune system

Which of the following statements is FALSE: A) The budding process is driven by the formation of matrix and capsid proteins forming a new viral particle underneath the cell membrane where envelope proteins are embedded B) Maturation of the HIV virus occurs before the virus buds off from the host cell C) The protease cleaves the gag proteins within the viral particle to form the final capsid structure D) The gag-pol complex has viral enzymes bound to it for packaging

B

Which viral enzyme is directly involved in incorporating HIV DNA into the host chromosome? A) protease B) integrase C) RdRp D) RT

B

Which viral protein is used to bind to the CD4 receptor? A) Hemaglutinin B) gp120 C) CCR5 D) Heparin sulfate

B

Which of the following is a distinct step in the reverse transcription of retroviral RNA? A) nicking of the template RNA B) template exchange C) initiation of synthesis of new template RNAs D) initiation of (+) DNA synthesis

B and D

What does RT make?

BOTH strands of viral DNA

How can HIV encode additional proteins?

has additional splicing mechanisms (and more ways of modifying host transcription)

After integration, what does HIV rely on for replication? (viral or host)

host proteins (including host polymerases)

What is the first step of retroviral integration?

conversion of viral RNA into DNA (enzymes such as reverse transcriptase do this)

What are 3 tests for HIV? What is the recommended first test (bold)? What test is confirmatory secondary?

-Ab test (Abs against HIV) (confirmatory) -*Ab/Ag test* (Abs against HIV and HIV itself [antigen]) -RNA/DNA test (viral RNA and copies of viral RNA in DNA)

What are common coreceptors for HIV and what cells have them?

-CXCR4 (T cells) -CCR5 (T cells, macrophages, monocytes, and dendritic cells)

What are 4 other possible modes of transmission?

-IV drug abuse -mother to child -accidental needle sticks -blood transfusions

What are 3 structural components of a simple retroviral genome? Give their function.

-LTR on 5' and 3': integration -viral coding region b/w LTRs: has all genes and proteins to be translated -proviral DNA when virus is inserted into host chromosome to make mRNA

What 4 things do all retroviruses have?

-enveloped with lipid membrane that surrounds capsid -matrix proteins underneath envelope (stability and structure) -viral glycoproteins which are transmembrane or surface -most have icosahedral nucleocapsids (HIV is more conical)

What do homozygous and heterozygous mutations result in?

-homozygous: resistance/immunity -heterozygous: slower disease progression

What modes of sexual transmission are most common?

-male to male (in US) -male to female (resource limited settings) -female to male (more rare)

How does the HIV genome differ from other retroviruses?

-more complex; encodes additional proteins (tat, rev, and nef proteins)

What are the 2 types of mRNA that are made and what do they encode?

-unspliced: gag-pol proteins -spliced: envelope proteins

How do retroviruses differ from other ss(+) RNA viruses?

1) 2 copies of RNA 2) RNA is coated with a nucleocapsid protein

What happens to HIV after entry?

1) RT uses host nucleotides to convert viral RNA to ssDNA (high error rate) 2) RT makes ssDNA to dsDNA 3) integrase takes dsDNA through pore into nucleus and nicks DNA for integration into host genome

Which of the following lentivirus proteins are generated from a spliced RNA? A) envelope proteins B) polymerase proteins C) gag proteins

A

When are HIV structural proteins processed?

AFTER virus is formed

What is the most common mode of transmission for HIV? A) IV drug use B) Sexual contact or intercourse C) Transfer from mother to child D) Blood transfusions

B

In which way is the retrovirus HIV unlike other ss(+) RNA viruses? A) Retroviruses are smaller than all other ss(+) RNA viruses B) Retrovirus RNA gets transcribed in the cytoplasm C) Retroviruses are enveloped while other ss(+) RNA viruses are not D) Retroviruses encode an RT to convert their RNA to DNA

D

Which detection method is best for early detection of HIV? A) They are all equally good for early detection of the virus B) Ab tests that detect the immune response made to the virus C) RNA/DNA tests that detect viral genomes D) Ab-Ag tests that detect the virus in the blood

D

Where are the envelope proteins made?

ER, then enter natural secretory pathway and go to cell surface joining with capsid to make new viral particle and bud off

What's the difference between HIV-1 and HIV-2?

HIV-1 is associated with AIDS in the US and worldwide -HIV-2 is more rare and associated with AIDS in W Africa and S Asia

What happens during acute infection?

R5 strain binds to CCR5 and enters different cells (like dendritic cells which are found on epithelial or mucosal tissue) and migrates to lymph nodes to infect more immune cells

What cells does HIV primarily infect? What are the receptors?

T cells (also other immune cells); CD4 on T cells (primary), chemokine coreceptor (CCR5)

What were the first retroviruses discovered?

cancer-inducing viruses (RNA rather than DNA)

How are envelope proteins generated in retroviruses?

cell makes a separate spliced mRNA that is translated to make envelope proteins (no suppression of stop codon)

What does the binding of CD4 induce?

conformational change in viral envelope protein that allow interaction with CCR5

What do retroviruses package _________ __________ inside their _____________.

essential enzymes; nucleocapsid

What does the binding of CCR5 trigger?

extension of fusion protein so HIV can enter cell via membrane fusion

What symptoms are present in the acute phase? How long is this phase?

flu-like symptoms; 12 weeks

What gp attaches to CD4?

gp120

How is HIV treated?

help live longer and healthier and reduce transmission, antiretroviral therapy (ART)

What does HIV and other retroviruses use to make its mRNA? (viral or host)

host RNA polymerase

Where does this processing of the gag-pol complex occur?

inside viral particle AFTER budding

What causes the lifelong infection of HIV?

integration of viral DNA into host chromosome

What do retroviruses do instead of making one long polyprotein?

makes several polyproteins: 1) translation of gag proteins 2) cleaved by proteases when stop codon is suppressed 3) gag pol precursor is formed and cleaved by proteases

What 2 proteins drive retrovirus budding from the cell?

matrix and capsid proteins

Are retroviral ss(+) RNA genomes immediatedly translated?

no

Is integration sequence specific?

no, it can happen in any chromosome

What are symptoms of AIDS?

persistent fever, fatigue, weight loss, diarrhea, high HIV in blood

What 3 proteins do retroviruses package in their nucleocapsid

reverse transcriptase, protease, and integrase enzymes

What does the high error rate from RT result in for HIV?

slighly different HIV strains targeting different cell types and altering viral tropism

What does HIV generate its envelope proteins from? Where does it get its envelope?

spliced mRNA; from external host cell membrane

What happens after the T cell gets low enough?

swollen Lymph nodes, hairy leukoplakia (white patch on tongue), oral candidiasis (yeast infection), leads to AIDS

What happens to the gag-pol complex?

translated to a polyprotein, then processed by packaged viral protease

Why was the discovery that these viruses were RNA rather than DNA surprising?

tumor formation results from permanent changes to the cell, which usually comes from DNA

What cells have CD4 molecules?

T helper cells, macrophages, and dendritic cells

How is HIV transmitted?

sexual intercourse

What is a provirus?

viral DNA that has been incorporated into the host genome

_________ (viral or host) enzymes convert HIV genome to dsDNA usable by __________ (viral or host) enzymes.

viral; host