Studies on role of dendritic cells in HIV infection

Abstract

AIDS was identified as a distinct clinical entity in year 1981 in United States. The virus that causes AIDS was isolated in 1983 and was given nomenclature as HIV in 1986. Subsequently two types of HIV (type 1 and type 2) were identified. It has been estimated that HIV-1 was probably transmitted from chimpanzee (Pan troglodytes) to humans in central Africa in early thirties whereas HIV-2 was transmitted to humans about 60 years ago from sooty mangabey (Cercocebus atys) monkeys of West Africa. HIV/AIDS is now major public health concern in many countries. UNAIDS global estimates indicate that the number of people living with HIV in 2008 globally was 33.4 million (31.1-35.8 million) and 2 million (1.7-2.4 million) people died of AIDS. Of the 2.7 million (2.4-3 million) people who were newly infected with HIV in 2008, (i.e. over 7400 new infections in a day) more that 96% are from low and middle income countries. Approximately 2.4 million (2 million–3.1 million) people in India were living with HIV in 2008 (UNAIDS 2009 report). The major hallmarks of HIV infection include destruction of helper CD4+ T cells and subsequent loss of immune competence. Considerable efforts have gone into understanding the mechanism by which HIV causes the disease and two major hypotheses have been forwarded, first, that HIV causes loss of CD4+ T lymphocytes by directly infecting and killing those cells. The second is that HIV infection indirectly impairs cell function and is based on the observation that uninfected and bystander cells are affected. A deeper understanding of viral replication and the reservoirs that contribute to it, and of how the virus-host interact with each other are important for understanding the basis of viral pathogenesis. The DC reservoir is the most enigmatic of all as DCs are among the first cellular targets of HIV-1 during sexual transmission. Dendritic cells (DCs) are most versatile antigen presenting cells that are central to induction and regulation of adaptive immune responses. DCs reside in different tissues and mucosal surfaces as immature cells and possess capacity to acquire, process and present antigens to T cells; induce tolerance in self reactive T cells, interact with B and NK cells and play a very significant role in antiviral innate Abstract of Ph.D. Thesis Meera Singh October 2010 immune response.