HIV Flashcards
Most common types of reteroviruses
HIV-1/2 and HTLV
Retrovirus genetic make up
Single-stranded, (+)-sense RNA with two copies.
- transcribes its own DNA via reverse transcription and implants it into host cells, causing lifelong exposure
Steps of HIV replication cycle
Virus attachment and fusion
Reverse transcription within host cytosol
Integration of reverse transcribed DNA into host DNA
viral transcription
Viral translation
Assemble, budding and maturation of the new virions
Cores structural proteins of HIV genome
P15/18/24
- generated via the Gag precursor (pr55)
- P24 is the most important since it is the immunological marker sued to determine that someone has HIV*
Viral enzymes of HIV genome
P10 (protease)
p32 (integrase)
PP 65/66 (reverse transcriptase)
Generated via the Pol precursor (p160)
Envelope proteins of HIV genome
GP120 (primary docking protein)
GP41 (transmembrane glyco protein)
- generated via the Env precursor (gp160)
Accessory proteins of HIV and their function
Tat = increases viral RNA synthesis
- required to transcribe enough viral RNA to generate an infection
Rev = transport full length RNA from nucleus
- required to package the RNA and make new virons
Nef = perturbs cell signaling and enhances infectivity
Vif/Vpr/Vpu = control cellular restriction factors
Attachment of the HIV virus
Mediated by gp120 and gp 41
- gp120 is hyper variable and often presents with mistakes when being transcribed due to reverse transcriptase not being able to fix mistakes.
- Makes it harder for adaptive immune system to make antibodies for it
Infects CD4+ cells only
- does this via binding to CD4 receptor and chemokines coreceptor
Coreceptors function to make gp41 bind more efficiently to the CD4 T cells
- CCR5, CXCR4
- must have both go 120:DC4 and GP41: CCR5/CXCR4 in order to enter cell*
Native Env Trimer
GP41
Gp120
V1/2
Which protein mediates entry of the HIV pathogen
GP41
When does the HIV virus become infectious?
Once protease cleavage occurs
- until this occurs, the HIV is in the immature variant form (cant infect)
- this occurs after the budding and the release stage.
What white cells are infected in HIV/AIDS
T helper cells (CD4)
Monocytes/macrophages
Three stages of HIV
Acute retroviral syndrome (HIV)
- transmitted via body fluids
- 2-3 month timeframe
- Ab to HIV negative with positive viral load
Prolonged asymptomatic state
- time between HIV and AIDS where chronic infection is progressing but Immune status is not low enough yet
Acquired immunodeficiency syndrome (AIDS)
- usually takes 10 years from HIV to develop
Ways HIV is spread
Unprotected sex
Anal sex
Pregnancy/breastfeeding
Sharing syringes or drug equipment
- only infectious if viral load is detectable and not controlled.*
Primary symptoms of acute HIV
Mononucleosis or flu-like symptoms
- fever
- lymphadenopathy
- malaise
- pharyngitis
When is HIV RNA and P24+ detectable in the host body and when is antibodies produced?
HIV RNA = at the time of infection
P24+ in blood samples = 20 days *This usually coincides with development of symptoms and class switching to IgG antibodies*
Antibodies = 45 days
What is the point in which AIDS is diagnosable?
When CD4 cells are 200/mm3 or lower
HIV screening
13-64 year olds should be screened at least once as a routine health care
- gay men need to be screened more frequently
Diagnosis of HIV infection
P24 core antigen test
- (+) = has it
RNA detection viral load
CD4+ count
- low numbers could mean HIV
Test for associated STIs
- gonorrhoeae/ chlamydia (+) increases chances of acquiring HIV
How it can be confirmed negative for HIV?
Wait 20 days after exposure and then run the tests
- negative for antibodies to HIV 1/2 and negative for p24 = NO HIV
common Symptoms of AIDS
Chronic fever
Weight loss
Persistent diarrhea
Lymphadenopathy w/ oral lesions
Fatigue
Pneumonia and other opportunistic infections
- only present when CD4 counts are lower than 200 cells/mm3 and not taking prophylactic drugs
Common opportunistic infections for AIDS patients
Pneumocystis jirovecii
Cryptosporidium
Cryptococcus
Candida
Cytomegalovirus
HHV-8
Usually start within 9-10 years of having HIV (right before or at the clinical stage of AIDS)
Common cancers that are more common in AIDS patients
Kaposi sarcoma
Non-Hodgkin lymphoma
Lymphocytic leukemia
Hodgkin lymphoma
Burkitt lymphoma
Liver cancer
Mouth/throat cancer
Categories of HIV therapeutics
Integrate inhibitors
Reverse transcriptase inhibitors
- block conversion of HIV RNA -> HIV DNA
Fusion/entry inhibitors
Protease inhibitors
Two types of reverse transcription inhibitors
Nucleoside
- binds directly to DNA chain being reverse transcribed and prevents it from finishing
Non-nucleoside
- denatures the reverse transcriptase enzyme
Most common antiretroviral therapy’s
Based on baseline resistance and co-infections
Requires life-long adherence
Usually requires at least 3 of the inhibitors
Types of HIV targets for treatment
Integrase inhibitors
Reverse transcriptase inhibitors
- both NNRTIs and NRTIs
Fusion/entry inhibitors
Protease inhibitors
PrEPs and PEP agents/regiments
Are both prophylaxis regiments for HIV used for people who have high chances of exposure
PrEPs (truvada) is for pre-exposure
PEP is for post-exposure
