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20 Cards in this Set

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AIDS
Acquired Immunodeficiency Syndrome --
• The great PANDEMIC of the second half of the 20th century… and beyond…?
• AIDS is caused by the Human Immunodeficiency Virus [HIV]
• AIDS was first described in 1979; the virus HIV was finally discovered in 1983 [Robert Gallo and Luc Montagnier]
• Testing of blood bank sera show that AIDS cases date from at least 1959 (Democratic Republic of the Congo) and that AIDS originated in Africa, then spread to Europe, then globally, …
Classification of HIV
• Classified in the Retrovirus group - It possesses Reverse Transcriptase, the enzyme that transcribes RNA into DNA
• Belongs to the virus family Lentiviridae - Produce slowly progressive, usually fatal conditions
• There are two major antigenic types - HIV-1 and HIV-2
- They are only ~40% identical at the genetic level
HIV-1 -
- There are 11 serotypes (A-O); B is the most common serotype in the USA.
- It is virulent
- Causes "Full-Blown AIDS"
- Spreading widely and rapidly
HIV-2 -
- Found predominantly in Western Africa
- It is less virulent [it rarely causes "full-blown AIDS"]
- It is not spreading as widely and rapidly as HIV-1
Origins of HIV 1
• Up to 1% of the human genome consists of "genetic fossils" of viruses that inserted their genes into the genome(s) of our ancestors [Science News 156:311(1999)]
- The gene Rev (50 copies/ human genome) - Human Endogenous Retrovirus K (HERV-K) first entered the genome of the old world monkey 30 million yr ago, then several dozen other times
- HERV-K is now "harmlessly" dormant in our genome and continues to produce proteins with unknown functions (e.g. in the placenta)
The River
book by edward hooper. - BBC journalist's research on the Africa Polio Vaccine Trials of the 1950's
- ~250,000 Africans were vaccinated
- He wrote that the live polio vaccine was made using cell cultures from the chimpanzee [Pan troglodytes] and the bonobo [Pan paniscus] - Not true
- Disproved by recent evidence
Origins of HIV 2
• HIV evolved in Africa from viruses that infect other primates and “jumped” into humans at least 3 times [via “bush meat”]
- The Los Alamos National Labs "Family Tree of HIV" - Computer analysis of HIV evolution predicted that HIV began to spread as long ago as 1930 (based on DNA sequences from the 1st 1959 isolate, until the development of a new strain in Thailand in 1987)
Simian Immunodeficiency Virus (SIV)
has been found in the chimpanzee
[Pan troglodytes troglodytes and P. troglodytes schweinfurthii]
- Different subspecies/populations in Gabon, Cameroon, and Equatorial Guinea are separated by rivers; they harbor different strains of SIV
- SIV is hypothesized to have been in chimps for at least 1000,000 yr
- SIV is hypothesized to be the source of HIV-1
- 2 SIV.cpz-infected chimps have been in captivity for 15 and 23 years, without developing an AIDS-like disease – SIV is kept under control by CD8+ lymphocytes [Science 283:857-60 (1999)]

• SIV.sm -
- HIV-2 has been traced to the SIV that infects the sooty mangabey monkey
Transmission of HIV Disease - Prevention of HIV Transmission
• Both HIV-1 and HIV-2 are spread through transfer of body fluids/tissue containing either free virus or infected cells:
- The main vectors of HIV transmission are blood, vaginal fluids, and semen
- But, HIV can also be present in tears, saliva, bronchial secretions, and milk
- And HIV can also be present in donated blood, blood products, or organs
Life Cycle of HIV-1
*Adsorption To Host Cell Receptors
*Fusion Of Viral And Cell Membrane Via Co-Receptors
* Uncoated
*Transcription Of Viral RNA into DNA
*Integrates Into The Host Cell Genome
*PROVIRUS
1.) Adsorption To Host Cell Receptors
high affinity binding of gp120 to CD4 [CD4 is present on the surface of several cell types, including TH cells (CD4+ lymphocytes) and monocytes].
- Monocyte - Macrophage lineage [including phagocytic cells such as dendritic cells and microglial cells of the CNS [HIV cannot form a productive infection in them, but infected monocytes are a source of persistent infection in the host]
- There are no T cells in the vagina or rectum; it is hypothesized that HIV binds to Dendritic Cells and "hitches a ride" to lymph nodes.
2.) Fusion Of Viral And Cell Membrane Via Co-Receptors
- Exposure of gp41 - homologous to the “fusion-inducing proteins” of other viruses
- gp41 embeds itself in the membrane of the host cell when host cell co-receptors remove the gp120 “cap” from gp41 [HIV hijacks the cell surface receptors to force its entry into its target cells] -
- ß-chemokine receptor [CCR5 (or CCR2 /3) on TH cells and macrophages]
[Science 276:51 (1997)]
- and later, as patients' immune system wears down, ß-chemokine receptor [CXCR4 - “fusion” on T cells]
- Cytomegalovirus [CMV], a herpes virus, may also serve as a cofactor - its US28 protein is present on the surface of CMV-infected cells [Science 276:1794 (1997)]
3.) Uncoated
Virion is Uncoated, releasing the viral RNA into host cell’s cytosol
4.)Transcription Of Viral RNA into DNA
Transcription Of Viral RNA into DNA [via reverse transcriptase which was complexed to the viral RNA within the virion]
5.)Integrates Into The Host Cell Genome
The Newly Synthesized Viral DNA Migrates To The Nucleus, there it Randomly Integrates Into The Host Cell Genome [via virion-associated integrase]
6.) PROVIRUS
The integrated virus, now called a PROVIRUS, may do a number of things:
• “Peacefully” persist in the host cell - few virus particles are produced; few host cells are killed
• Form syncytia - Direct cell-to-cell spread, forming giant, multi-nuclear cells that soon die
• Become “Activated” so that -
- The integrated viral DNA can be transcribed into viral RNA via host transcription factors and host RNA polymerase
- The new RNA genome will also serves as mRNA that is translated into viral structural and regulatory proteins
- Viral glycoproteins are synthesized, glycosylated, and processed by the ER and Golgi apparatus
- Progeny viral RNA and structural proteins assemble at the cell surface.
- Budding of massive numbers of virions from the cell surface results in cell lysis
Clinical Stages of HIV Infection
Definition of AIDS - An HIV-infected individuals who has <200 CD4+ T cells/L of blood or a CBC with <14% CD4+ lymphocytes
- Some patients rapidly develop clinical AIDS; die within 2-3 years
- Some patients remain relatively healthy for at least 10 years post infection
- In majority of patients HIV infection progresses to AIDS in 8-10 years
CDC Classification System for Stages of HIV-Related Conditions
• Early Viremic Stage (Acute Retroviral Syndrome)
• Asymptomatic Stage
Chronic Symptomatic Stage – Immunosuppression
Early Viremic Stage (Acute Retroviral Syndrome)
- 2-8 weeks after exposure to HIV, primary HIV infections present with an abrupt onset of a febrile illness resembling acute mononucleosis
- Symptoms include: headache, myalgia, pharyngitis, lymphadenopathy, rash, weight loss, nausea, and diarrhea
- Usually resolves within 1-2 weeks
- Symptoms coincide with a high-grade viremia
- "Viral Load" of 85,000 copies of HIV RNA/mL of blood
- A drop in the number of circulating CD4+ lymphocytes may occur
- "Seroconversion" - HIV-specific Ab is then detectable
Asymptomatic Stage
- A long and variable asymptomatic period (6 months to 10 or more years)
- Followed by a slow, progressive decline in CD4+ cell numbers and an increase in CD8+ cells
- During this period, HIV can be found in lymphoid organs and in tissue macrophages
- Viral replication is being "kept in check" by the immune system
- "Viral Load" of 20,000 copies of HIV RNA/mL of blood