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GENETIC DIVERSITY OF HIV.
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MODES OF TRANSMISSION OF AIDS VIRUS Most infections with HIV are transmitted through mucosal surfaces such as anal and vaginal mucosa. Transmission through vaginal mucosa has been demosntrated in a model of Simian immunodeficiency virus (SIV) infection. Infection of rhesus monkeys (Macaca mulatta) has proven a suitable model for the infection of human with HIV in terms of transmission, viremia and disesae. Rhesus macaque were inoculated intravaginally with SIVmac251, and then killed 2, 5, 7, and 9 days later. SIV was present in the lamina propria of the cervicovaginal mucosa. The localization and the phenotypic characteristics of the infected cells suggested that the cells that harbor the virus were dendritic cells. Within 2 days after inoculation, the infected cells were found in the paracortex and subcapsular sinus of the draining internal iliac lymph nodes. This was quickly followed by systemic dissemination of SIV. Presence of virus in the blood could be seen as early as on day 5 after inoculation of the virus. In other cirumstances, the entry of HIV is through exposure to blood such as blood transfusion, by sharing needles among the drug addicts or by transplacental passage of the virus. Oral infection is also a well documented route for transmission of HIV in neonates. Neonates can acquire the disease by breast feeding. Presence of blood in gastric aspirates of neonates born to HIV infected mothers has also been incriminated as a risk factor in the transmission of HIV. In addition, seroconversion of adults after oral-genital sex has been observed. These findings indicate that the mucosa of the gastrointestinal tract serves as a portal of entry for HIV. A new finding clearly supports these observations. In a study published in the June 7, 1996 issue of Science, Baba et al describe that non-traumatic oral exposure of adult Macaques to cell-free SIV also results in AIDS. Although the minimal dose required for achieving systemic infection by oral route was about 800 times more than that required by intravenous injection of the virus, this does was 6000 times lower than the minimal dose required after rectal exposure. These findings suggest that oral sex poses a clear risk for acquiring AIDS. REFERENCE:
PROGNOSIS OF HIV INFECTION The prognosis of HIV infected individuals is quite variable. In most adults, the average time between the entry of the virus into the body and development of AIDS is 10-11 years. However, in certain individuals (about 20%), AIDS is manifested within 5 years of infection. Yet another 12% of individuals remain free of AIDS for 20 years. Many laboratory tests have been developed to assess the prognosis of AIDS, however, by far the most reliable indicator is the percentage or the absolute number of CD4+ cells. Another parameter used for prognostication is the amount of HIV-1 RNA in the plasma soon after seroconversion. Shortly after entry of the HIV into the body, there is a burst of viremia. The subsequent immune response results in a steady-state level of the viral particles in the plasma. This number which is variable in various individuals, serves as the predictor of long term outcome of the disease. In the May 24, 1996 issue of Science, Mellors et al describe that the vial load as measured by a branched DNA signal amplification assay was a reliable prognostic marker in HIV infection. The risk of AIDS and death from the disease was directly related to the plasma viral load at the time that the patient entered into the study. As compared to the number of CD4+ T cells, the plasma viral load seems to be a better predictor of progression of AIDS and death. REFERENCE: Mellors JW, Rinaldo Jr CR, Gupta P, White RM, Todd JA, Kingsley LA: Prognosis of HIV-1 infection predicted by the quantity of virus in plasma. Sicence 272, 1167-1170, 1996 HIV-1 ENTRY CO-FACTOR CD4 on human cells acts as the primary receptor for HIV-1. The hybrids of non-human and human cells showed that presence of an additional factor is required for the membrane fusion events that allow entry of HIV-1 into cells. Presence of this co-factor is also required for fusion of the CD4+ cells with cells that express the glycoprotein of the HIV envelope, Env. With the use of a novel functional complementary (cDNA) cloning strategy, the identity of this co-factor that is designated as "fusin" has been revealed. Feng et al, in the May 10, 1996 issue of Science report that fusin is a putative G protein-coupled receptor with seven transmembrane domains. The mRNA level of fusin correlated with the permissiveness of various human cell lines to HIV-1. In addition, presence of both fusin and CD-4 on cells rendered them highly premissive to HIV-1. Antibodies to fusion blocked cell fusion and infection with HIV-1 ith normal CD+ human cells.The protein encoded by fusin gene for shows 37% amino acid identity with the receptor for IL-8 which is a chemkine of the C-X-C class of molecules The gene for fusin is located on chromosome 7 in the vicinity of the C-X-C chemokine receptor (Cocci et al, 1995). It is interesting to note that C-C chemokines RANTES, MIP-1 alpha, and MIP-1 beta, produced by CD8CD4+ cells, suppress HIV-1 infection in vitro (Cocci et al, 1995). REFERENCE: Feng Y, Broder CC, Kennedy PE, Berger EA: HIV-1 entry cofactor: fuctional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science 272, 872-877
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Pathogens including HIV mutate and such mutations represent a challenge in the diagnosis, treatment and surveillance of this disease. There are highly divergent strains of human immunodeficiency virus (HIV) that are not reliably detected by a number of commonly used diagnostic tests. This indicates that there is a need to institute methods for tracking these variants of HIV. Hu et al describe the implications of the rapid development of HIV mutation and general guidelines for surveillance of AIDS. Only the institution of such guidelines will allow us to monitor and track the global dissemination of HIV. 
