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BMEN 515 Lecture Notes - T Helper Cell, Simian Immunodeficiency Virus, Regulatory T Cell

Biomedical Engineering
Course Code
BMEN 515
William Huddleston

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The Natural History of the HIV/AIDS Epidemic
List of worst epidemic in human history according to the number of deaths:
o Influenza-50 to 100 million deaths-across the globe
o Black Death (1347-1352)-took 30%-50% of the European population-about25 million lives
o New World small pox-released in 1520 by European conquistadores-decimated Native American populations across two
AIDS is among the worst epidemics in human history
o Was first recognized in 1981
o So far infected more than 65 million people
o 25 million have already died
o By year 2020, a total of 90 million lives would have been claimed by AIDS
o According to World Health Organization, AIDS is responsible for about 4.9% of all deaths worldwide
o Sub-Saharan Africa is mostly affected by this epidemic
HIV establishes a new infection when a bodily fluid holding the virus, usually a blood or semen, carries it from an infected person
directly onto a mucous membrane or into the bloodstream of an uninfected person
o Can be passed during heterosexual sex, homosexual sex, oral sex, needle sharing, transfusion with contaminated blood
products, childbirth, and breastfeeding
An HIV infection can be acquired only from someone else who already has it!
What is HIV?
Like all viruses, HIV is an intracellular parasite that cannot reproduce on its own
o It invades specific types of cells in the human immune system
o It uses enzymatic machinery and energy of these cells to make copies of itself, killing the host cells in the process
Figure 1.5 (Pg. 7) contains the life cycle of HIV in detail.
o The life cycle includes an extracellular phase and an intracellular phase
o During the extracellular phase, the virus moves from one host cell to another, and can be transmitted from host to host
o Extracellular form of a virus is called a virion, or virus particle
o During intracellular or parasitic phase, the virus replicates
HIV initiates its replication phase by latching onto two proteins on the surface of a host cell
HIV binds to two surface proteins on the target cell called CD4 and coreceptor
This binding fuses the virion’s envelope with the host’s cell membrane and spills the contents of the virion into the
These contents include the virus’s diploid genome (two copies of a single-stranded RNA molecule) and 3
o Reverse transcriptase- transcribes the virus’s RNA genome into DNA
o Integrase- splices the DNA genome into the host cell’s genome
o Protease- which plays a role in the preparation of new viral proteins
In HIV and other retroviruses, flow of genetic information is different than in cells and in viruses with DNA
In retroviruses, genetic information does not follow the familiar route from DNA to mRNA to proteins
o Instead it flows from RNA to DNA, then to mRNA to proteins
Once HIV’s genome is inserted into the host cell’s chromosomes, the host cell’s RNA polymerase transcribes the viral
genome into mRNA, and the host cell’s ribosomes synthesize viral proteins
New virions assemble in the host cell cytoplasm, then bud off the cell membrane and enter the bloodstream
There, the new virions may find another cell to infect in the same host, or be transported to a new host
o Significant feature of HIV’s life cycle is that the virus uses the host cell’s own enzymatic machinery, its polymerases,
ribosomes, and tRNAs in almost every step
How Does HIV Cause AIDS?
HIV parasitizes immune system cells, particularly helper T cells. After a long battle against the virus, the immune system’s supply of
helper T cells is badly depleted. Because helper T cells play a crucial role in the response to invading pathogens, this leaves the host
vulnerable to a variety of secondary infections.
Through research on how SIVsm (simian immunodeficiency virus) in monkeys, it was concluded that the host’s own immune response
contributes to the development of immunodeficiency
o Human HIV patients treated with antiretroviral drugs plus the immunosuppressant cyclosporine maintained higher helper T
cell counts than control patients treated with antiretrovirals alone
T cells derive from stem cells in the bone marrow
These stem cells generate precursors that mature into naive T cells in the thymus
Naive T cells are activated in lymph nodes
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