Retroviruses and HIV Pathogenesis

Question 1

Human T-cell Lymphotropic virus (HTLV) is the causitive agen in what two diseases?

Answer 1

1) HTLV-1 can cause Adult T-cell Leukemia/Lymphoma (ATLL). This is mostly in people who are infected before the age of 20
2) HTLV-1 (and potentially 2) can cause HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) but only around 2% of cases

Question 2

The majority of people infected with HTLV are (symptomatic/asymptomatc)

Answer 2

Asymptomatic

Question 3

How is HTLV transmitted?

Answer 3

1) Breastfeeding
2) Sex
3) IV drug use

Note: this would be considered a non-contagious disease along qith HIV

Question 4

HIV, like all retroviruses, carries what?

Answer 4

Two strands of the same RNA message in their virion. Some say they are diploid

Question 5

HIV makes this +ssRNA into a ________ with viral reverse transcriptase

Answer 5

viral DNA copy (called the provirus)

Question 6

What happen’s once HIV makes a viral DNA copy (provirus)?

Answer 6

Integrase will then integrate the (proviral) DNA into the cellular chromosome. This viral DNA stays integrated into the cellular DNA for the life of the cell

Question 7

List the HIV Genes

Answer 7

-gag
-pol
-env

Question 8

What is the protein from the HIV gag gene?

Answer 8

p24 is the capsid protein; detection of p24 is used in some HIV diagnostic tests

Question 9

What is the protein from the HIV pol gene?

Answer 9

-The protease cleaves the viral polyprotein and matures the virion
-Reverse transcriptase is an RNA-dependent DNA polymerase and makes proviral DNA from the viral +ssRNA
-Integrase puts the proviral DNA into the cell chromosome

Question 10

What is the protein from the HIV env gene?

Answer 10

-HIV is an enveloped virus. The viral envelope glycoproteins gp120 and gp41
-Gp120 is the envelope glycoprotein that binds the receptors, CD4, and the secondary receptors, CCR5 or CXCR4
-Gp41 is the envelope glycoprotein that has a fusion domain. It fuses the lipid bilayer of the virus with the plasma membrane, allowing the capsid the enter the cytoplasm of the cell

Question 11

What kills HIV?

Answer 11

HIV is an enveloped virus. Detergents and drying kill it. However, the accepted way to clean off contaminated surfaces is with a 10% bleach solution or another virucidal

Question 12

T/F: There is a lot of viral diversity in a person infected with HIV

Answer 12

True! This is due to the reverse transcriptase error rate and the fact that reverse transcriptase has no proofreading activity.

HIV’s diversity is why there needs to be drugs from two classes of antiviral for treatment.

Question 13

What happens during the acute phase of HIV infection?

Answer 13

During the acute phase, a lot of virus is
being produced in the body, and some
people feel like they have the ‘flu’ or
mononucleosis.

Question 14

What happens during the chronic phase of an HIV infection?

Answer 14

The immune system
reduces the amount of virus to a lower
level during the long chronic phase.

Question 15

When are people more likely to spread HIV - during the acute or chronic phase?

Answer 15

Actue phase

Question 16

During infection, people infected with HIV may also have __________

Answer 16

Lymphadenopathy (swollen lymph nodes)

Question 17

What is the receptor for HIV?

Answer 17

CD4

Question 18

Most cells HIV infects are ________, but HIV can also infect macrophages, microglial cells, and dendritic cells

Answer 18

CD4+ T cells

Question 19

What is the secondary receptor of HIV?

Answer 19

Either CCR5 or CXCR4

Question 20

Upon initial infection, HIV almost always uses the ______ receptor only.

Answer 20

CCR5

Only one virus infect a person; that virus is CCR5 restricted. **This is why people with a deletion in CCR5 are mostly protected from infection with HIV

Question 21

Where HIV establish infection?

Answer 21

In the gut-associated lymphoid tissue (GALT) and remains in the GALT during chronic infection.

Question 22

What does HIV infection of the GALT result in?

Answer 22

Infection of the GALT early on in infection results in dysbiosis in the gut (more
pathogenic types of bacteria than harmless commensals in the gut) and leakage of bacterial products like
LPS into the blood. This leakage is a significant contributor to the chronic immune activation seen in
people living with HIV.

Question 23

During acute infection, HIV can establish an infection in the _____

Answer 23

brain

Question 24

It is during this acute phase that ______ infected HIV cells are established.

Answer 24

Latenly

**These cells are very long-lived; if antiviral drugs are removed, the virus from these cells will reseed the infection

Question 25

During the chronic HIV infection stage, there is a gradual loss of ______, leading to the loss of a functional immune system and the development of acquired immune deficiency syndrome (AIDS)

Answer 25

CD4+ T cells

Question 26

What happens without HIV treatment?

Answer 26

Without treatment, over 95% of people infected with HIV will develop AIDS and die from opportunistic
infections, cancer, or complications of HIV infection. The average time from infection until developing
AIDS is eight years

Question 27

____ cells do not function as well in chronic HIV infection

Answer 27

B

Question 28

Chronic HIV infection in the brain can continue resulting in cognitive decline; the worst manifestation is ________

Answer 28

HIV-associated dementia (HAD)

Question 29

A person with HIV has AIDS if the CD4 T cell count is below _______ or….

Answer 29

200 CD4 cells/ul or an AIDS-defining opportunistic infection is diagnosed

Question 30

During chronic HIV infection, what happens when the CD4 count gets too low?

Answer 30

Opportunistic infections start

Question 31

What happens over many years without treatment of HIV chronic infection?

Answer 31

Lymph node architecture destruction

Question 32

What is HIV treatment called?

Answer 32

-Highly Active Antiretroviral Therapy (HAART)
or
-combination Antiretroviral Therapy (cART)
or
-Antiretroviral Therapy (ART)

**They mean the same thing

Question 33

**T/F: To treat HIV, there needs to be drugs from two different classes of antiretrovirals

Answer 33

TRUE

Question 34

What is the treatment goal for HIV?

Answer 34

To reduce the virus to undetectable levels

Question 35

The lower the CD4 T cells are before HIV treatment starts…..

Answer 35

1) The less likely that the CD4 counts will rebound to pre-infection levels
2) The less likely the lymph node architecture will return to normal
3) POSSIBLY could be more damage to the brain due to active replication of the virus. In general, many people who are infected with HIV show a cognitive decline.

Question 36

When should you start HIV treatment?

Answer 36

As early as possible!

Question 37

What are the potential benefits of starting HIV treatment early?

Answer 37

-Less immune dysfunction:
1) Lymph node architecture is not destroyed
2) Potentially reduced dysfunction in the GALT
3) Less thymus loss
4) CD4 counts can reach uninfected levels
5) Lower co-morbidities

-Less severe neurological effects, most people under ART with suppressed viral loads do not show progression in cognitive decline