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HIV is commonly seen in blood, semen, vaginal fluids, and breast milk. It is also present in saliva and tears at very low levels. The HIV is transmitted by the following ways.
CD4+ T lymphocyte is the main target for HIV. During productive infection it will lyses the T lymphocyte. It also infects NK cells (natural killer cells), CD8+ killer T cells, macrophages, cells of the nervous system and dendritic cells. It requires receptors and co- receptors for entry in to the cell. The CD4 is the major receptor which is present on T lymphocyte at high level and also present on macrophage at low level. CXCR4 and CCR5 are co-receptors present in T lymphocyte and macrophage respectively.
AIDS is caused by HIV. It is characterized by decreasing the number of CD4+ T helper lymphocyte and the immune system becomes weaken.(1)
Cytopathic Effect (CPE):
CPE is defined as any detectable changes in host cell during viral infection. HIV has the following CPE on host cell.
Formation of Syncytia:
Syncytia is defined as the formation of giant cells by the fusion of infected and uninfected cells. This fusion is mediated by viral env proteins that are expressed on the surface of infected cells. Then the surface env protein is able to bind to CD4+ receptor of uninfected neighboring cell result in fusion of plasma membrane which leads to form syncytia. Finally death can occur.(1)
Cell death due to accumulation of extra chromosomal viral DNA:
During early stages of HIV infection the unintegrated viral DNA accumulates in cytoplasm invitro. These accumulation is toxic to the host cell and it leads to cell death. But this process in invivo is not known.(2)
Binding and entry of HIV into host cell causes membrane discontinuities and pores. So the host cell lost the control of influx of cations with water. It leads to cell death.(2)
HIV infected macrophage produce cytokines (TNFÎ±). The TNFÎ± is responsible for apoptosis in both infected and uninfected cells. The HIV infected macrophage can also loss their ability to produce IL-1 and it leads to apoptosis of infected CD4+ cells.(2)
HIV infection can be divided into three phases. They are primary HIV infection, chronic asymptomatic phase and AIDS.
1. Primary HIV infection:
It is the period between after infection and before the development of antibodies. During this period the virus can able to replicate rapidly and it lasts for few weeks to months. In this period the viruses detected in blood, central nervous system and lymphatic system. It also enters other tissues. The signs and symptoms are different from person to person. Some individuals may not show any symptoms. Some individuals show symptoms like flu and mononucleosis. These are also known as acute retroviral syndrome. But those symptoms are disappeared within a month.
2. Chronic asymptomatic phase:
In this phase the signs and symptoms does not occur. This phase lasts for long period about ten years. The infected individuals can be divided into three groups based on viral load, number of CD4+ T cell, production of antibodies and development of disease.
Typical Progressor: This group can be characterized by virus can replicate continuously, high level of virus in blood, depletion of CD4+ T cell count. Because of depletion of CD4+ T cells the opportunistic infection may occur.
Rapid Progressor: Infected individual develops AIDS within five years.
Slow Progressor: Infected individual cay not develops AIDS for more than fifteen years.
During this phase full blown AIDS appears. If AIDS patients do not take treatment, they will die within two to three years. In this phase the CD4+ T cell decreased at very low level. So the bodyâ€™s immune system becomes weakens and also loss their ability to fight against other infection. So increased level of opportunistic infection can occur which is responsible for death. Systamatic non- Hodgkins lymphoma and wasting syndrome may appear on AIDS patients.(1)
Immune response against HIV infection:
Humoral immune response:
During acute infection the immune system of body produced antibodies (Ig G).These molecules are present in blood and other body fluids. There are three types of processes involves in antibody mediated fight against HIV. They are neutralization, ADCC and complement dependent cytotoxicity.(2)
Neutralising antibodies have the ability to neutralize the infectivity nature of the virus. There are several kinds of neutralizing antibodies appeared.
Anti V3 antibody: The variable region 3 (V3) of the gp120 is recognized by immune system as epitope to produce antibodies. These antibodies prevent the fusion of infected and uninfected cells. It is a strain specific antibodies.
CD4 blocking antibody: This antibodies prevent the binding of gp120 to CD4+ receptor. It is not a strain specific antibodies. It reacted with virus broadly.(3)
The antibody against the gp41 and gp120 have the ability to induce ADCC. The natural killer cells or macrophages identified the antibody- antigen coated cells. The Fc portion of antibody binds to Fc receptor of natural killer cells or macrophages. After binding they are killed by perforin mediated or by apoptosis.(2)
Complement mediated cytotoxicity:
After binding of antibody to the antigen the complement fixation takes place. There are series of steps involved in complement fixation and finally the cell will lyses.(2)
When the antigen presenting cells present antigen at their surface via class II MHC molecules, the T cell receptor of CD8+ CTL recognize these foreign antigen. Finally they are killed by perforin mediated death.(3)
Dendritic cells: These cells are acting as antigen presenting cells. It ingest and processed the antigen. Then the processed antigen present at the surface via MHC molecules and activates Tcells and B cells.(2)
1.Teri Shors; Understanding Viruses; Jones and Bartlett publishers, Massachusetts, 2009.
2.Jay A. Levy; HIV and the pathogenesis of AIDS; ASM press, Washington,DC,2007
3.John E Coffin; Stephen H Hughes; and Harold E Varmus; Retroviruses; Cold Spring Harbor, Newyork,1997.