Microbiology - Moffat - HIV Replication and Pathogenesis and Blair - AIDS

Question 1

What are the two most common routes of infection for HIV?

Answer 1

Unprotected sex

Needle sharing

Question 2

Who are the most at-risk groups for HIV transmission?

Answer 2

Gay and bisexual men (63%)
Heterosexuals (25%)
IV drug users (8%)
Gay and bisexual men who also inject drugs (3%)
**she will ask a question on this

Question 3

What does HIV having a small Ro mean?

Ro

Answer 3

It means that one exposure is usually not enough to infect a person
For example, a large Ro would be influenza

Question 4

T/F: Women are more likely than men to become infected.

Answer 4

True

Question 5

When is PAP most effective?

Answer 5

Hours to days after exposure

Question 6

What cells does HIV first infect?

Answer 6

Lymphoid cells embedded in the vaginal and rectal epithelium, then spreads to the lymph nodes and blood

Question 7

T/F: HIV is a diploid RNA virus.

Answer 7

True, but each copy of the virus may be different.
HIV is a ssRNA (+) strand retrovirus
“lentivirus” - slow to cause disease

Question 8

When do syncitia form?

Answer 8

Late during infection
Depends on the host response if they form or not
New cell tropism
CXCR4 receptor (T cells)

Question 9

What was the first and is the major target of antiretrovirals?

Answer 9

Reverse transcriptase

Protease is the next big target

Question 10

Read the HIV lifecycle overview.

Answer 10

1. Attachment and fusion
2. Uncoating
3. Reverse transcription
4. Migration of genome to nucleus
5. Integration into host chromosome
6. mRNA and genome synthesis
7. mRNA export
8. Viral protein synthesis
9. Genomic RNA export
10. Spliced mRNA synthesis
11. Viral membrane protein synthesis
12. Protein maturation
13. Protein accumulation at plasma membrane
14. Virion assembly at plasma membrane
15. Budding
16. Virion maturation (immature virions are not yet infectious)

Question 11

Human susceptibility to HIV infection depends on what protein?

Answer 11

Presence of CCR, chemokine receptor, which can be found on macrophages and T cells. Some people have genetic variants of this that make them less susceptible to HIV infection.

Question 12

What is the primary obstacle to eradicating HIV from a person?

Answer 12

Latency after the viral genome has incorporated itself into the host genome
Best characterized reservoir = infected resting memory CD4+ T cells, but other reservoirs can include the brain, macrophages, hematopoietic stem cells.

Question 13

Phase I of HIV replication ends with integration into the host genome. What does Phase 2 consist of?

Answer 13

Lytic replication using host RNA Polymerase II

Question 14

T/F: Discontinutation of HAART allows viral relapse from latent reservoir.

Answer 14

True

Question 15

How is the HIV virion made infectious?

Answer 15

The viral protease packaged in the virion must cleave Gag into its three subunits (MA-CA-NC) to form infectious particles. Therefore, protease therapy blocks infectivity of HIV to other cells

Question 16

What happens in HIV syncytium formation?

Answer 16

HIV infected T cells can fuse with uninfected T cells.
**this is a major cause of immunodeficiency.
Not all strains form syncytia, but those that do are more virulent.

Question 17

When does HIV become AIDS?

Answer 17

Classified as T cells

Question 18

What are the possible symptoms of AIDS?

Answer 18

Encephalitis
Meningitis
Retinitis (ie from CMV)
Pneumocystis Pneumonia
Tumors (pulmonary, GI, skin)
Kaposi Sarcoma (HHV8)
Progressive multifocal leukoencephalopathy, PML (brain)
Esophagitis, esophageal candidiasis
Chronic Diarrhea
Oral hairy leukoplakia (tongue)
Seborrheic Dermatitis
Nodular prurigo
Opportunistic infections ie TB (multiple organs), Thrush, toxoplasmosis etc.

Question 19

T/F: Direct killing of T cells by HIV replication accounts for the immune dysfunction.

Answer 19

FALSE. The immune system seems to take a harder hit than the loss of T cells would suggest.
Activated T cells are even thought to be responsible for releasing cytokines that kill their own kind.

Question 20

Why are defective HIV virions harmful to the host?

Answer 20

Toxicity

Question 21

When are HIV antibodies first seen?

Answer 21

Within 3-12 weeks of infection

Question 22

At what CD4+ and viral load is treatment with HAART recommended.

Answer 22

At any level. However non-adherence is a major obstacle especially to early ART therapy.

Question 23

Besides RT and protease, what are some other targets of HIV therapy?

Answer 23

Integrase inhibitors
CCR5 and CXCR4 inhibitors (entry level)
Fusion inhibitors