HIV human immunodeficiency virus By Susi Smith Prevalence Between 39 and 44 million people around the word live with AIDS 60 of people with AIDS live in subSaharan Africa Between 2 8 and 3 5 million people died with AIDS in 2004 AIDS is a pandemic comparable to the bubonic plague Infection Risks When pricked by a needle used by an infected person less than 1 200 Post exposure within 24 hours a person should start a 28 day regimen of HIV drugs which prevents HIV infection almost 99 After 72 hours the effectiveness of the regimen decreases to 52 3 chance of getting infected per sexual interaction with use of a condom The presence of cervical ectopia use of oral contraceptive or pregnancy raises the infection risk History of HIV AIDS CDC in 1981 noticed unusual clusters of Kaposi s sarcoma in gay men in NY and San Francisco which led to the disease to be called GRID Gay Related Immune Deficiency By 1982 the disease was apparent in heterosexuals and was renamed AIDS Acquired Immune Deficiency AIDS was not recognized as a new clinical syndrome until 1981 However researchers examining the earlier medical literature identified cases appearing to fit the AIDS surveillance definition as early as the 1950s and 1960s The virus is thought to native to monkeys in Africa specifically of Western Africa http hivinsite ucsf edu InSite page kb 01 03 S1 2X http hivinsite ucsf edu InSite page kb 01 03 S1 2X Transmission Vaginal Intercourse Anal Intercourse 10x higher infection rate then vaginal intercourse because of tissue tear Oral Intercourse Blood Transfusion risk greater than 90 if sample is already infected Needles tattoos injections Infected mother to the infant through Pregnancy placenta Birth and breastfeeding Symptoms AIDS as when a person with HIV has either a CD4 cell count below 200 A person contracts an opportunistic infection Kaposi s Sarcomas Wasting caused by HIV infection Toxoplasmosis of the brain Salmonella septicemia recurrent Pneumonia recurrent Lymphoma Burkitt s immunoblastic primary of brain primary central nervous system lymphoma Disease caused by Mycobacterium tuberculosis Herpes simplex Candidiasis of bronchi trachea lungs or esophageal Cervical cancer Invasive medical Diagnosis The HIV test used by Americans quantitatively tests for a CD4 cell count lower than 200 per microliter of blood However countries that cannot afford the HIV test use symptomatic diagnosis set out by the CDC and the World Health Organization in 2004 An individual must have prolonged fevers for a month or more weight loss of over 10 and prolonged diarrhea This leads to over diagnosis of HIV in these countries http en wikipedia org wiki AIDS CDC Classification of HIV Category 1 500 cells mm3 or CD4 28 Category 2 200 499 cells mm3 or CD4 14 28 Category 3 200 cells mm3 or CD4 14 CD4 T lymphocyte counts per microliter of blood The percentages were derived from correlating counts and percentages from 7 different data sources AIDS and Children Methods that prevent transmission from a mother to a child 1 Strict adherence to antiretroviral drugs 2 Cesarean Section 3 Formula The earlier stage of HIV infection during pregnancy the better chance the baby will be unaffected 1 in 4 babies born from HIV infected mothers are infected Infection http www avert org pictures aidshiv2 htm HIV infects the T Helper cell because it has the protein CD4 on its surface HIV needs to use CD4 to enter cells it infects This is why the T helper cell is referred to as a CD4 lymphocyte Correlation between CD4 and HIV http upload wikimedia org wikipedia en thumb 3 34 500px Hivtimecourse png Infections throughout the Body Within the inflammatory cells of the infection T cells Site of replication shifts to lymphoid tissues Lymph nodes Spleen Liver Bone marrow Macrophages and Langerhans cells become reservoirs and sites of replication but do not die themselves Infected lymph nodes infect the follicular dendritric cells FDC which infect the CD4 cells percolating through the node The FDC do not die The virus replicates quickly because infected T cells have a half life of two days Therefore there is a rapid host cell turnover Structure of HIV Spherical 120 nm in diameter env proteins make the spikes on the membrane Conical capsid Electron dense core HIV Life Cycle HIV enters the CD4 helper T cell by bonding with CXCR4 Fusin a cofactor helps HIV bind to the membrane GP41 the viral protein penetrates the cell and the reverse transcriptase integrase protease and various other enzymes are injected into the cell Using reverse transcriptase and the T cell s machinery the HIV replicates its RNA into DNA Integrase then inserts the viral DNA into the T cell s genome The host is fully infected but not producing proteins so it not infectious latent stage The T cell s transcription factor NF Kappa B causes the viral genes to be transcribed once the T Cell becomes activated by fighting an infection Splicing then occurs producing regulatory proteins tat and rev Rev then inhibits the splicing From the full length mRNA gag and env are made The full length RNA HIV s genome attaches to gag The virus reforms in a cholesterol rich region under the membrane and then buds outside the cell Once outside the virus matures cleaving gag into smaller proteins and becomes infectious Reverse Transcriptase Reverse Transcriptase RNA DNA RNA Occurs in the cytosol Has a lipid coating surrounding the capsid wash your hands Reverse transcription does not undergo proofreading leading to a mutation every 2000 integrated nucleotides These mutations create variants of the HIV virus making the creation of a vaccine very hard Retroviral Genes gag group specific antigen makes the coneshaped viral capsid pol polymerase codes for viral enzymes reverse transcriptase integrase and viral protease env envelope makes surface protein gp120 and transmembrane gp41 enabling HIV to fuse to CD4 cells HIV Genes tat eliminates the hairpin structure in RNA by phosphorylating CdK9 CycT This increases transcription and creates a positive feedback loop vpr is involved in getting the viral RNA into the nucleus of the T cell It causes the cell to stop growing stimulating an immune dysfunction rev creates a rev Response Unit that exports the HIV RNA into the cytoplasm before it is spliced It is also a positive feedback loop nef down regulates CD4 on the T cell inhibiting response to infectious agents vif helps HIV infect other cells though it is still unclear how It is thought that it interferes with
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