HIV Flashcards
Source of HIV-1/AIDS infection
The oldest ancestor of HIV-1 to date is from the Democratic Republic of Congo (DRC) most likely from the Bushmeat trade in which infected chimps were slaughtered and contaminated blood mixed with human.
With the invention of air travel, this spread out of Africa and to the rest of the world (pandemic)
Source of HIV-2
Sooty Mangabeys infected with simian immunodeficiency virus (SIV) are the source of HIV-2 infection of humans
LESS pathogenic than HIV-1. The disease takes a LONGER time & it is LESS severe.
Primarily isolated to the west coast of Africa
People living with AIDS 2017
36.9 million
highest concentration in Sub-Saharan Africa
Deaths due to AIDS 1980-2015
35-40 million
New trend of HIV infection
Has been decreasing (-18%)
Current Epidemiology of the Disease
It is a disease of both men & women worldwide.
In the United States – it is primarily still gay men & drug abusers.
Worldwide – it is a disease more or less equally distributed between men & women, because it is just in the society more general.
In Men – it is still predominantly transmitted to men from men to men through man-to-man sex.
In Women – it is predominantly transmitted from men to female sex.
So, men are the vectors in humans (as you might imagine, because it is the man who is predominantly sharing the bodily fluid with the recipient (the semen - that is carrying the virus = the primary mode of transmission))
Injection drug use is also a substantial contributor (of course, even more in women. Because, the men on women sex does not transmit it as readily as the man on man sex act…Because, anal receptive intercourse, the recipient is at a higher risk than with the vaginal tract in women with the differences in the tissues. There is more likely to be microabrasions/ tearing during anal receptive sex & that leads to infection.
HIV Transmission
Sex, Blood, Breast milk/ Vaginal Birth, IV drug use
NOT SALIVA
Virology of HIV-1 Infection
1) Enters through break in mucosa and goes to nearest site of the lymph nodes
2) There, it will start to replicate in the lymph node (because lymph nodes have all these immune cells (the t cells especially where the virus likes to replicate in CD4 Tcells)
3) The virus will spread throughout your body. You’ve got CD4 T cells in all your mucosal tissue leading to an exponential RISE in the viral load.
4) Emergence of flu-like symptoms. You may feel under the weather and the virus is going to peak
5) Around the same time, your immune system kicks in and your cytotoxic T cells (CD8 killer T cells) kick in & they start fighting the virus and our viral load DROPS radically.
6) Then you go along for year after year and eventually you DEPLETE the immune system sufficiently to where you CANNOT fight opportunistic infections
And, your get opportunistic infections (ex. Pneumonia) – they will kill you, NOT the virus!
Structure of HIV
2 capsids (one that is icosahedron and an inner cone shaped capsid)
Within the capsid 2 RNA genomes and its own reverse transcriptase
Has a lipid envelope
Immature HIV viron buds out of cellular membrane and through protease cleavage, cleaves into active form (cone shaped)
Drug Target Types
Reverse Transcriptase Inhibitors
Protease Inhibitors
Fusion Inhibitors
Intergrase Inhibitors
used in combination for increase efficacy
RT inhibitors
Failed cancer drugs which block reverse transcriptase function
Protease inhibitors
Inhibitors of the protease enzyme which cleaves the polyproteins into their mature subunits
Fusion (Entry) Inhibitors
They block the virals from getting into the cell by blocking the spikes / their ability to cause fusion with the cell
Integrase Inhibitors
(inhibitors of the integrase enzyme)– that block the virus from integrating into your chromosome.
Cells that are infected by HIV virus
Activated CD4+ T cells - these cells make most of the virus
Resting CD4+ T cells - these are few but are often latently infected and cannot currently be eliminated. (If a patient stops HAART, virus from these cells will begin replicating.)
Macrophages - can be persistently infected for long periods and apparently don’t die from infection, though their function is impaired.
HIV can reach the brain when monocyte/macrophages pass the blood-brain barrier and enter as microglial cells.
