Retroviruses - HIV / AIDS Flashcards
What is the definition of a retrovirus?
A virus which uses a reverse transcriptase to transcribe a ssRNA to a dsDNA
Why is HIV called a Lentivirus?
Lenti - means slow
It is a slowly progressing disease
What are the two types of HIV and which one is more virulent?
HIV-1 and HIV-2. HIV-2 is more like SIV, but HIV-1 is worldwide and highly virulent
What are the three tropisms of HIV? What is HAD?
M-tropic - Macrophages - binds CCR5 as coreceptor
T-tropic - CD4+ T cells - binds CXCR4 as coreceptor
Microglia - results in the neurologic disorders such as HIV-associated dementia (HAD)
What is the primary receptor of HIV for all the forms?
CD4 - the tropism only changes the co-receptor
What is the first stage of HIV infection called and how does this relate to infectiousness? How does this relate to antibodies and CD4 count?
Acute Retroviral Syndrome - within 1-3 months of HIV infection. Flu-like symptoms, with highest viral loads until the patient dies.
HIV loads will fall as anti-HIV antibodies develop. CD4 cells will also recover as this happens
What is the second stage of HIV and what is happening during this time?
The clinical latency stage, typically lasting 8-10 years
It is the asymptomatic stage where the CD4 cell temporarily rises, and then HIV copy number declines. There will be a slow trend of CD4 count downward during this stage.
What is the “viral set-point”?
The stabilized plasma concentration of virus after the peak of primary infection, it is the equilibrium met between cytotoxic T cell killing and viral replication in CD4 cells.
What is the cutpoint for development of AIDS? Lasts 2-3 years
CD4+ count is less than 200 cell / mL, making you very vulnerable to opportunistic infections.
Lasts 2-3 years typically
What are long-term non-progressors?
Minority of peak infected with HIV - low virus levels with elevated CD4+ count and no antiretroviral treatment
What are three ways to be a long-term non-progressor?
- Mutations in CCR5 - slows progression
- Higher levels of CCR5-binding ligands - compete with HIV
- APOBEC3 - high levels of proteins which counteract reverse transcriptase
What is the HIV virus structure?
Two identical + sense RNA strands, spherical capsid, enveloped retrovirus
How many genes are in the HIV genome and what classes are they?
9 genes:
3 structural
2 Regulatory
4 Accessory
What is the function of gp120?
Part of viral envelope, binds to CD4 and CCR5 or CXCR4
What does gp41 do with respect to gp120?
gp41 is another envelope protein, penetrates through cell membrane and facilitates fusion between virus and human cell
This fusion releases the capsid into the cytoplasm
What is the function of Pol? What proteins does it yield?
Cleavage of Pol precursor yields the Protease, Reverse Transcriptase, and Integrase enzymes
What does HIV do once it’s capsid is in the cell?
Viral RNA is reverse transcribed by RT into dsDNA. Integrase enzyme gets it into the genome
What proteins are responsible for transcription and export?
The two regulatory proteins: Tat and Rev
Tat = enhances RNA transcription (transcriptional activator) Rev = prevents RNA splicing in the nucleus before export
Where does HIV-1 virus assembly begin? What genes are first transcribed?
At the plasma membrane, Gag and Pol precursors are transcribed first
When does release happen?
The three structural proteins Env, Gag, and Pol assemble with the viral RNA genome and acquire their envelop by passing out of the host membrane
What happens in the maturation step?
Outside of the cell, with envelope acquired, the viral protease (made from Pol protein in the cell) cleaves precursor Gag and Pol proteins to make mature infectious virus particle
What proteins are a part of Gag?
Matrix
Capsid
Nuclear Capsid
What is Env protein before cleavage?
Env = gp160, cleaves into gp120 (surface) and gp41 (transmembrane)
What is the definition of HIV accessory proteins?
They are non-essential. Virus can replicate in vitro without them, but they are needed for in vivo pathogenesis
What are the four HIV accessory proteins?
Nef
Vif
Vpr
Vpu
What is Nef?
Accessory protein for immune evasion by downregulating CD4 and MHC Class 1
e = evasion
What is Vif?
Virion infectivity factor - counteracts host cytidine deaminases which degrades reverse transcribed viral DNA
What is Vpr?
Viral protein R - infection of nondividing cells such as macrophages, induces a cell cycle arrest and apoptosis
R = arrrrrrrrrrrrrrrrrrrrrrrrest
What is Vpu?
Viral Protein U - Promotes virus bUdding
What are the cellular reservoirs of HIV?
Infected CD4+ cells, macrophages, and DCs
Even ASTROCYTES!
What is it so difficult to fully eradicate HIV?
Anatomical reservoirs = sanctuaries. Such as the CNS, male genital tract, and lymphoid tissue. Antivirals cannot get to these sites and their are immuneprivileged. Cannot cross BBB
How is HIV diagnosed?
ELISA or Western blot (for protein)
What is HAART / its definition?
Highly active anti-retroviral therapy Combination of 3 or more drugs from at least 2 classes: 1. Nucleoside analogs RT inhibitors 2. Non-nucleoside analog RT inhibitors 3. Entry inhibitors 4. Protease inhibitors 5. Integrase inhibitors
What is the first identified human onco-retrovirus? What family is it in?
Human T-cell Leukemia Virus (HTLV)
Belongs to Deltavirus genus
What are the two main diseases caused by HTLV-1?
Adult T-cell Leukemia (ATL)
Tropical spastic paraparesis / HTLV-1 associated myelopathy (TSP/HAM)
What is the transmission of HTLV-1?
Vertical, sexual, or blood / IVDU
Where is HTLV-1 prevalent?
Australia, Caribbean, South America, Central + West Africa, South Japan
What is the treatment for HTLV-1?
IFN-alpha and zidovudine
What provides temporary relief from TSP?
Zidovudine, danazol (a steroid), and vitamin C
