Viral STI's

Question 1

What are the two serotypes of HIV?

Answer 1

HIV-1 and HIV-2

HIV-1 is predominant worldwide

Question 2

HIV-2 is ____ likely to lead to lead to AIDS than HIV-1

Answer 2

LESS

Question 3

What is the retrovirus lifecycle?

Answer 3

1. Attachment
2. Fusion
3. Reverse Transcriptase of RNA genome
4. Integration
5. Genome Replication + Transcription
6. Budding
7. Maturation

Mature Virion!

Question 4

How does HIV attach to cells?

Answer 4

gp120 binds to CD4

CD4 found on T-lymphocytes, monocytes, macrophages

Question 5

Conformational change in gp120 allow binding to coreceptors____

Answer 5

CCR5
CXCR4

Question 6

What is R5-trophic HIV?

Answer 6

Uses CCR5 as coreceptor

Transmitted from person to person and predominantly early in disease

Efficiently infects monocytes/macrophages and microglia

Question 7

What genome does HIV have?

Answer 7

RNA

Question 8

What are the physical characteristics of the HIV virus itself?

Answer 8

Capsid portin p24
Reverse transcriptase polymerase
Fusion protein gp41
Attachement protein gp120

Has envelope, matrix, nucleocapsid, genome

Question 9

What is X4-trophic HIV?

Answer 9

Uses CXCR4 as coreceptor

40% of patients transition from R5 to X4 viruses during course of disease -> associated with rapid progression to AIDS

Question 10

What are HIV-CCR5 deletions? What occurs when they are homozygous or heterozygous?

Answer 10

Subset of population contain deletion in region of CCR5 gene that affects its binding to gp120

Heterozygous deletion = longer asymptomatic period before onset of AIDS

Homozygous deletion = no infection with R5 trophic viruses (X4 trophic HIV can infect!)

Question 11

What is the function of gp41 of HIV?

Answer 11

Mediates fusion between viral envelope and plasma membrane

Question 12

The process of ________ uses a encoded enzyme within the virion and produces a linear dsDNA copy of RNA HIV genome.

Answer 12

Reverse transcription

Question 13

What allows for rapid evolution of HIV over course of disease? What are the consequences?

Answer 13

Hight error rate of reverse transcription

Need multi-drug therapy

Question 14

How is HIV integrated?

Answer 14

dsDNA copy of genome moves into nucleus of cell

Viral integrase causes DNA copy of genome to be incorporated into the host DNA (provirus)

Provirus is then transcribed and replicated and remain in cell

Question 15

Progeny HIV virions exit the infected cell by _______ through the plasma membrane at lipid rafts

Answer 15

Budding

Question 16

How does HIV mature after being integrated into host?

Answer 16

Viral protease cleaves the gag and gag-pol viral polyproteins

Essential for infectivity of the virion

Question 17

What is essential for infectivity of the HIV virion?

Answer 17

HIV maturation and specifically the protease cleavage events

Question 18

How is HIV transmitted?

Answer 18

Sexual
Perinatal
Exposure to contaminated blood or bodily fluids

Question 19

What is the most common and efficient method of transmission?

Answer 19

Heterosexual (male to female) transmission

Question 20

When does mother to child transmission of HIV most commonly occur?

Answer 20

Most at birth

Question 21

Where can accidental exposure occur with HIV?

Answer 21

Healthcare workers

Question 22

What is the progression of HIV?

Answer 22

Acute infection
Chronic lymphadenopathy
Sub-clinical immune dysfunction
Skin and mucous membrane immune defects
Systemic immune deficiency

Question 23

What do you see during the acute phase of the infection of HIV?

Answer 23

rise in virus p24 antigen or RNA

Question 24

What drops as HIV progresses?

Answer 24

CD4 T cells

Question 25

What are symptoms of HIV similar to? What are other symptoms?

Answer 25

Infectious mononucleosis Rash - faint Burst of viremia May not have detectable levels of antibodies at this time

Question 26

What occurs during the initial burst of viremia of HIV?

Answer 26

Immune response curtails the level of virus in blood so antibody rising Virus levels decrease

Question 27

What is occuring during chronic HIV infection?

Answer 27

Low level of viremia HIV escape immune system Patients often aymptomatic

Question 28

How does HIV escape the immune system?

Answer 28

Antigenic drift of gp120 Inactivation of key elements of immune response Cell to cell fusion

Question 29

How does HIV progress to AIDS?

Answer 29

Reduction in CD4 T cells - leads to copious budding, interference with cellular processes Reduced ability to fight other microbial infections

Question 30

What are HIV associated infections? x6

Answer 30

Oral Hairy Leukoplakia - EBV Pneumonia - mycobacterium tuberculosis, pneumocystitis carinii Thrush - candida albicans CMV retinitis - CMV Neoplasms - Kaposi's (HHV-8), B cell lymphomas Diarrhea - Cryptosporidium, isospora belli

Question 31

What are targets for diagnosis of HIV?

Answer 31

p24 Ag immunoassay Antibodies to HIV anti-gp120 Viral genome nucleic acid test (NAT)

Question 32

HIV-1/1 antibody differential immunoassay tests for ____ and helps differentiate between those two

Answer 32

HIV-1 antibodies HIV-2 antibodies

Question 33

HIV 1/2 antigen/antibody combination immunoassay detects _____ and helps with screening for HIV diagnosis

Answer 33

HIV - 1 antibody HIV - 2 antibodies HIV p24 antigen

Question 34

HIV nucleic acid tests detect _____ and these genomes are detectable at earlier times of the infection than antibodies

Answer 34

HIV RNA genomes

Question 35

What anti-HIV drug classes are available for use?

Answer 35

Entry inhibitors: gp120 attachment inhibitor, co-receptor antagonist, CD4 post-attachment inhibitor, fusion inhibitors Protease inhibitor Integrase strand transfer inhibitors Reverse transcriptase inhibitors

Question 36

How do fusion inhibitors work?

Answer 36

Bind to gp41 and prevent conformation change needed for fusion of the viral envelope with the plasma membrane

Question 37

How does chemokine coreceptor antagonists work?

Answer 37

bind to co-receptors and prevent its interact with gp120 Maraviroc is a CCR5 antagonist - limited to use in patients that possess R5 trophic HIV

Question 38

How do gp120 attachment inhibitors work?

Answer 38

binds to gp120 near CD4 binding site to prevent interaction with CD4

Question 39

How do CD4 post-attachment inhibitor work?

Answer 39

human monoclonal antibody binds to CD4 extracellular domain 2, resulting in steric hinderance of conformational change required for HIV fusion and entry Does NOT impact binding of CD4 to gp120

Question 40

This drug is incorporated into growing DNA chain during provirus synthesis and causes chain termination

Answer 40

Nucleoside inhibitors (NRTIs)

Question 41

This drug binds to reverse transcriptase and inhibits its activity

Answer 41

Nonnucleoside inhibitors (NNRTIs)

Question 42

This drug blocks the integration of the DNA copy of the viral genome into the cellular genome

Answer 42

Integrase inhibitors

Question 43

This drug inhibits viral protease and leads to production of immature, defective HIV particles

Answer 43

Protease inhibitors

Question 44

What is the therapeutic goal for HIV?

Answer 44

Reduce viral load as low as possible for as long as possible

Question 45

___________ involves combination therapies, greatly increases the lifespan of HIV infected patients, and can cause issues like toxicity, compliance, and resistance.

Answer 45

Highly Active Antiretroviral Therapy (HAART)

Question 46

What is available for opportunistic infections in HIV patients?

Answer 46

Prophylactic treatments

Question 47

What is the preferred combination ARV (anti-retroviral) therapy for initial therapy?

Answer 47

1 II + 1-2 NRTIs

Question 48

How do we prevent HIV across common groups?

Answer 48

General public - educate about sexual behavior and transmission Accidental health care exposure risk reduced - prophylactic antivirals Mother to infant spread - C section, antiviral tx of mom and child, refrain from breast feeding

Question 49

Is there a vaccine for HIV?

Answer 49

NOOOO