Human Retroviruses and HIV Pathogenesis

Question 1

What is human T cell lymphotrophic virus (HTLV) cause of?

Answer 1

2 diseases!
- adult T-cell leukemia/lymphoma (only HTLV-1)
- HTLV-1 associated myelopathy/tropical spastic paraparesis (HTLV-1 and more with HTLV-2)

Question 2

How is HTLV transmitted?

Answer 2

• breastfeeding (25%)
• sex
• IV drug use (10-16% of IV drug users in US are positive)

Question 3

What type of virus is HIV?

Answer 3

retrovirus (2 strands of same RNA message in their virion… diploid)

Question 4

What are the main genes were concerned about regarding HIV?

Answer 4

• gag: p24 is capsid protien: detection of p24 is used in some diagnostic tests
• pol: portease cleaves viral polyprotein and matures virion
• env: HIV is an enveloped virus and viral envelope glycoproteins are gp120 and gp41

Question 5

What is the importance of gp120 and gp41?

Answer 5

gp120: envelope glycoprotein that binds the receptors, CD4, and secondary receptor (CCR5 or CXCR4)

gp41: envelope glycoprotein that binds has a fusion domain and fuses lipid bilayer of virus with plasma membrane allowing capsid to enter the cytoplasm of cell

Question 6

Why is there a lot of viral diversity in a person infected with HIV?

Answer 6

• reverse transcriptase error rate and it has no proofreading activity

Question 7

Why are people with a deletion in CCR5 mostly protected from HIV infection?

Answer 7

• because HIV uses a secondary receptor and it is almost always CCR5 (not CXCR4)

Question 8

What is happening during the acute phase in HIV?

Answer 8

• lots of virus is being produced in body with flu like symptoms and swollen lymph nodes

Question 9

In which phase are people most likely to spread HIV?

Answer 9

acute phase (7 to 26 times more likely)

Question 10

What is the receptor for HIV?

Answer 10

• CD4 T cells
• but also can infect macrophages, microglial cells, and dendritic cells

Question 11

T/F: Not everyone will go onto chronic HIV infection once infected

Answer 11

False!
If infected, everyone goes on to a chronic infection

Question 12

Where does HIV establish infection?

Answer 12

• gut-associated lymph tissue (GALT)
• remains in GALT during chronic infection and results in dysbiosis in the gut causing leakage of bacterial products like LPS in blood and is the contributor to the chronic immune activation seen in people living with HIV

Question 13

T/F: During acute infection, HIV can establish an infection in the brain

Answer 13

True!
due to infection of macrophages or microglia and can cause dementia

Question 14

When should you start HIV treatment?

Answer 14

• ASAP
• study showed patients who started ART before counts reached 350 CD4 cells were less likely to have serious AIDS defining event

Question 15

Why is HIV incurable?

Answer 15

• the latent reservoir in the acute phase because it can’t be detected by standards assays and don’t know its happening but replicating at low levels