Retroviruses and HIV Pathogenesis Flashcards
Human T-cell Lymphotropic virus (HTLV) is the causitive agen in what two diseases?
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
The majority of people infected with HTLV are (symptomatic/asymptomatc)
Asymptomatic
How is HTLV transmitted?
1) Breastfeeding
2) Sex
3) IV drug use
Note: this would be considered a non-contagious disease along qith HIV
HIV, like all retroviruses, carries what?
Two strands of the same RNA message in their virion. Some say they are diploid
HIV makes this +ssRNA into a ________ with viral reverse transcriptase
viral DNA copy (called the provirus)
What happen’s once HIV makes a viral DNA copy (provirus)?
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
List the HIV Genes
-gag
-pol
-env
What is the protein from the HIV gag gene?
p24 is the capsid protein; detection of p24 is used in some HIV diagnostic tests
What is the protein from the HIV pol gene?
-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
What is the protein from the HIV env gene?
-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
What kills HIV?
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
T/F: There is a lot of viral diversity in a person infected with HIV
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.
What happens during the acute phase of HIV infection?
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.
What happens during the chronic phase of an HIV infection?
The immune system
reduces the amount of virus to a lower
level during the long chronic phase.
When are people more likely to spread HIV - during the acute or chronic phase?
Actue phase
During infection, people infected with HIV may also have __________
Lymphadenopathy (swollen lymph nodes)
What is the receptor for HIV?
CD4
Most cells HIV infects are ________, but HIV can also infect macrophages, microglial cells, and dendritic cells
CD4+ T cells
What is the secondary receptor of HIV?
Either CCR5 or CXCR4
Upon initial infection, HIV almost always uses the ______ receptor only.
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
Where HIV establish infection?
In the gut-associated lymphoid tissue (GALT) and remains in the GALT during chronic infection.
What does HIV infection of the GALT result in?
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.
During acute infection, HIV can establish an infection in the _____
brain
It is during this acute phase that ______ infected HIV cells are established.
Latenly
**These cells are very long-lived; if antiviral drugs are removed, the virus from these cells will reseed the infection
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)
CD4+ T cells
What happens without HIV treatment?
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
____ cells do not function as well in chronic HIV infection
B
Chronic HIV infection in the brain can continue resulting in cognitive decline; the worst manifestation is ________
HIV-associated dementia (HAD)
A person with HIV has AIDS if the CD4 T cell count is below _______ or….
200 CD4 cells/ul or an AIDS-defining opportunistic infection is diagnosed
During chronic HIV infection, what happens when the CD4 count gets too low?
Opportunistic infections start
What happens over many years without treatment of HIV chronic infection?
Lymph node architecture destruction
What is HIV treatment called?
-Highly Active Antiretroviral Therapy (HAART)
or
-combination Antiretroviral Therapy (cART)
or
-Antiretroviral Therapy (ART)
**They mean the same thing
**T/F: To treat HIV, there needs to be drugs from two different classes of antiretrovirals
TRUE
What is the treatment goal for HIV?
To reduce the virus to undetectable levels
The lower the CD4 T cells are before HIV treatment starts…..
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.
When should you start HIV treatment?
As early as possible!
What are the potential benefits of starting HIV treatment early?
-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
