HIV Replication and Pathogenesis

Question 1

When, where and who exposed humans to HIV

Answer 1

1902-1921 in Cameroon

Chipanzees

Question 2

What are the most common methods of transmission of HIV?

Answer 2

Unprotected sex with an infected partner

Sharing needles with infected person

Question 3

What are the almost eliminated risk factors for the transmission of HIV?

Answer 3

Transmission from infected mother to fetus

Infection from blood products

Question 4

What is the order of individuals who are infected with HIV?

Answer 4

63%– Gay and Bisexual men
25%– Heterosexuals
8%– Injection drug users
3%– Gay and Bisexual men who also inject drugs

Question 5

With respect to ethnicity, who is most susceptible to an HIV infection?

Answer 5

African American males–> females
Then hispanic males–> females
Then white males–> females

Question 6

With respect to age, who are the individuals who are most susceptible to an HIV infection?

Answer 6

young people ages 13-24

Question 7

Who are the most susceptible to an HIV infection?

Answer 7

young, gay black men

Question 8

What does the HIV infection first infect in order to spread throughout the body?

Answer 8

lymphoid cells embedded in the vaginal and rectal epithelium—> spread to the lymph nodes and blood

Question 9

What are the features of HIV?

Answer 9

RNA virus
Retroviridae
Lentinvirus--slow to cause dz
ssRNA, + strand
Two copes in each virion (diploid)

Question 10

What does HIV bind early on in the infection?

Answer 10

HIV binds to CCR5 coreceptor–> macrophages

Non-synctium inducing

Question 11

What does HIV bind late in the infection?

Answer 11

HIV binds CXCR4 coreceptor –> T cells

synctium inducting

Question 12

Describe attachment and fusion of HIV…

Answer 12

Viral membrane has transmembrane and surface domains

SU–binds CD4 and chemokine receptors–causing conformational change in TM

Fusion peptide on TM–inserts in target cell and induces virus entry

Question 13

What determines the susceptibility to HIV infection?

Answer 13

Presence of CCR

Question 14

What occurs after attachment of the HIV and before reverse transcription of the ssRNA genomes to DNA?

Answer 14

Attachment then membrane fusion

Uncoating occurs and the capsid partially disintegrates

Question 15

What does HIV use in the cytoplasm to begin reverse transcriptase?

Answer 15

Deoxynucleotides (dNTPs)

RT enzyme–which is error prone

Question 16

After reverse transcriptase occurs and the ssRNA is now DNA, what is the DNA genome attached to and what is its role?

Answer 16

HIV protein Integrase—> has nuclear localization signal that directs it to the nucleus

Question 17

What serves as the primer for DNA synthesis from the HIV ssRNA?

Answer 17

tRNA bound to ssRNA is a primer

Question 18

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

Answer 18

HIV provirus integrates into the host chromosome–creating a reservoir of latent virus throughout the body and latency is the primary obstacle to eradicating the HIV

Question 19

What marks the end of Phase I of HIV replication?

Answer 19

Integration

Question 20

What marks the start of Phase II of HIV replication

Answer 20

Viral and cellular transcription factors bindig to the promotor in the LTR and recruiting RNA Pol II–> mRNAs transcribed, spliced, and exported to the cytoplasm

Question 21

HIV mRNAs that are translated on ribosomes form what?

Answer 21

Gag-Pol precursor

Question 22

Short mRNAs encode what?

Answer 22

the Environment for viral attachment and fusion

Translated in the rough ER

Question 23

What cleaves the integral membrane proteins used for attachment and fusion?

Answer 23

host proteases–> cleaves into SU + TM domains

Target for therapy

Question 24

When the Virions are formed from the budding off of the PM are they infectious?

Answer 24

NO–these are immature virions

Question 25

What causes the immature virions to become infectious mature virions?

Answer 25

HIV protease cleaves Gag into its subunits–results in capsid assuming its trapezoidal shape in the mature virion

Question 26

What do some antiretroviral drugs target to prevent the formation of mature virions?

Answer 26

Target the protease that cleaves the Gag into subunits creating the mature virion

Question 27

What does ENV do for the virus?

Answer 27

allows attachment and entry into T cells and macrophages

Also–can fuse infected T cells with uninfected ones–> syncytium formation

Question 28

What is lethal to T cells and is one cause of immunodeficiency?

Answer 28

Syncytia

Question 29

How does syncytium formation occur?

Answer 29

ENV causes infected T cells to fuse with uninfected T cells

Question 30

What results in the immune dysfunction that allow many dz. to arise in HIV patients?

Answer 30

Progressive loss of T helper and memory cells

Question 31

What is the only treatment for AIDS-related diseases?

Answer 31

Antiretroviral therapy–restores immunity

Question 32

What cells are infected during the initial phase of HIV infection?

Answer 32

CD4+ and CCR5+ cells

Question 33

What does ENV allow the HIV to infect? and what does this change?

What increases and decreases as AIDS progresses?

Answer 33

CD4+ and CXCR4+ cells

Changes the course of the disease and is a sign that immunological control (CD8+ T cells) is waning and the risk of AIDS is increasing

Viral load starts to climb and CD4+ T cells drop as AIDS progresses