HIV

Question 1

Retroviruses genome and strucutre

Answer 1

+RNA

enveloped

Question 2

important enzyme of retroviruses

Answer 2

Contain reverse transcriptase enzyme

- Copies RNA into DNA

Question 3

chronic nature of retroviruses

Answer 3

Cause chronic disease long after infection
- Due to integration of viral DNA into host
chromosome

Question 4

cause of AIDS

Answer 4

HIV (human immunodeficiency virus) is a retrovirus
that causes AIDS (acquired immunodeficiency
syndrome)

Question 5

overall decline of HIV

Answer 5

newly infected and deaths related to HIV are decreasing

Question 6

retrovirus capsid geometry

Answer 6

conical

Question 7

important envelope glycoproteins of retroviruses

Answer 7

gp41 and gp120

Question 8

provirus

Answer 8

DNA copy of viral RNA

DNA copy is inserted into the host genome

Question 9

HIV adsorption and penetration:
initial and late infection?
tropic nature?

Answer 9

M tropic (initial infection):
cells of macrophage lineage
Receptor/coreceptor: CD4 and CCR5

T tropic (later during infection):
T cells
Receptor/coreceptor: CD4 and CXCR4

Question 10

HIV adsorption mechanism

resistance?

Answer 10

Viral ENV protein gp120 binds to cellular receptor CD4 and to coreceptor CXCR4 or CCR5
Coreceptor interaction essential for gp41 contact and viral fusion with host cell.
Small number of resistant people - lack the coreceptors

Question 11

HIV penetrance

Answer 11

due to membrane fusion promoted by gp41, facilitated with coreceptor binding gp120
gp41 undergoes conformational change

Question 12

HIV genome replication parts

Answer 12

3 parts

1: synthesis of viral DNA copy
2: integration into host genome
3: transcription of viral DNA into more RNA

Question 13

part of 1 of HIV genome replication

Answer 13

Part 1: synthesis of viral DNA copy

Cellular tRNA used as a primer by reverse transcriptase

Several steps are required to create a double-stranded DNA copy of the positive sense, single-stranded RNA genome

Reverse transcriptase (RT) synthesizes one strand of DNA using viral RNA as the template.

Reverse transcriptase (RT) synthesizes the other strand of DNA using the newly created viral single DNA strand above as the template.

Question 14

importance of RT

Answer 14

RT enzyme is the major target for anti-HIV drugs

RT enzyme is error prone (1 error every 10000 nts!) ~1 error per genome, allows immune evasion

Question 15

HIV genome replication part 2

Answer 15

part 2: integration of viral DNA copy into host cell genome

Promoted by viral integrase enzyme

Question 16

HIV replication part 3

Answer 16

part 3: transcription of integrated viral DNA copy to create more viral RNA for assembly
Viral DNA is transcribed into RNA by host cell RNA polymerase II

Question 17

HIV protein expression and viral assembly

Answer 17

Viral RNA serves as mRNA for translation AND Viral RNA serves as the viral genome that is packaged into virions

Translation creates viral polyproteins, cleaved by proteases to mature sizes

Viral assembly occurs at plasma membrane. Virions acquire their membrane by budding of nucleocapsids from the plasma membrane.

Question 18

HIV accessory factors, important ones?

Answer 18

mod host cell functions

nef and vpu

Question 19

nef

Answer 19

decreases expression of MHC class I molecules on the surface of an
infected cell, preventing killing by cytotoxic T cells

Question 20

vpu

Answer 20

reduces cell surface CD4 expression and enhances viral release

Question 21

Long terminal repeats (LTRs) of the HIV genome

repsond to? create?

Answer 21

Transcriptional promoter (upstream LTR) and terminator (downstream LTR)

Promoter responds to host cell signals and can also be relatively dormant, creating the latent state that is an important characteristic of HIV

Question 22

HIV entry
routes?
enters as?

Answer 22

Virus may enter through:
microabrasions on mucosal surfaces
needle punctures (IV drug users)
intact mucosal surfaces

Virus may enter as:
part of an infected cell (macrophage, lymphocyte, spermatozoa)
free virus

Question 23

HIV replication during the chronic phase of infection after burst of viral replication that occurs during initial infection, cell populations

Answer 23

99% infected cell are CD4 Tcells with less than 1% being macrophages and resting CD4 cells
the less than 1% populations are responsible for viral latency

Question 24

initial HIV pathogenesis

Answer 24

Note initial contact is with macrophage lineage cells.
Infect/stick to dendritic cells
transport to lymph node - contact with CD4 T cells for chronic effects

Question 25

chronic HIV pathogenesis

Answer 25

loss of DTH mediated by CD4: important for controlling fungal and intracellular pathogens
(bacterial and viral)

Question 26

neurological symptoms of chronic HIV possibly from?

Answer 26

basis is not well understood

• possibly due to viral infection of neurons
• possibly release of substances by other cells that promote inflammation in brain

Question 27

viral load, cd4 count and Ab level in HIV

Answer 27

initial high viral load will fall as a result of Ab response, but CD4 levels fall slowly before increase in viral levels later on with a decreased Ab

Question 28

criterion for AIDS.

Answer 28

<200 CD4 T-cell/mm3 is the

Patients with higher CD4 Tcell counts are also considered to have AIDS if they display AIDS indicator
conditions

Question 29

AIDs indicators conditions

Answer 29

Candidiasis of the bronchi, trachea, or lungs
Candidiasis, esophageal
Kaposi sarcoma
Mycobacterium avium complex (MAC) or Mycobacterium kansasii, disseminated or extrapulmonary
Mycobacterium tuberculosis, pulmonary or extrapulmonary
Mycobacterium, other species or unidentified species, disseminated or extrapulmonary
Pneumocystis jiroveci (formerly carinii) pneumonia (PCP)

Question 30

Transmission of HIV

Answer 30

Transmission occurs by direct exposure of persons bloodstream to body fluid containing virus. HIV is found in the blood, semen, or vaginal fluid of someone who is infected with the virus.

Question 31

HIV and casual contact

Answer 31

not transmitted by casual contact (touching, etc.) (or even kissing, sneezing, bug bites, etc.)

Question 32

HIV and healthcare workers’ risk

Answer 32

There is a risk for health care workers but transmission even through needlestick is poor
(less than 1% of exposures show seroconversion)

Question 33

AIDS defined

Answer 33

• progressive destruction of CD4+ cells leads to collapse of immune system
• patient susceptible to opportunistic infections (see AIDS indicator conditions)

Question 34

Central nervous system disease also

associated with AIDS

Answer 34

dementia

Question 35

AIDS-related cancer

Answer 35

• Kaposi’ s sarcoma

– caused by human herpesvirus 8

Question 36

HIV treatments

Answer 36

– antiviral agents
• nucleoside analogue reverse transcriptase (RT) inhibitors
• nonnucleoside RT inhibitors
• protease inhibitors
• Fusion-penetration inhibitors (target gp41)

Question 37

HIV Vax

Answer 37

none, ongoing search

Question 38

HIV evasion of immune response

Answer 38

plasma virus will continually evolve with replication error by RT, causes neutralizing Ab to act as a selective pressure against different antigenic variants

if Ab from a later period of infections were used with earlier plasma viruses better neutralization could be seen

Question 39

Other human retroviruses

diseases?

Answer 39

human T-cell lymphotropic viruses (HTLVs) -I, -II, -III, and -IV

HTLV-I: causes adult T-cell leukemia and lymphoma
II,III and IV: no known diseases