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  • Topic: HIV, AIDS, Antiretroviral drug
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  • Published : March 16, 2013
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POTENTIAL TARGET FOR HIV ANTIRETROVIRAL THERAPY

ABSTRACT

HIV was discovered to be a life threatening disease in 1983, since then scientist have been progressively trying to develop antiretroviral therapy. Many drugs have been introduced to fight against HIV, but each of the drug have some level of toxicity or drug resistance to it, Which is why novel targets have been identified that can serve as antiretroviral therapy. Potential targets are explored from all the stages in HIV life cycle here. A clear insight about how this target works against HIV and complications faced by each target are reviewed. Genomics and development of new vaccines is a very new area of studies for HIV inhibition. Although this is not much successful right now but it is defiantly a step towards fighting HIV in future.

INTRODUCTION

Acquired immunodeficiency syndrome (AIDS) is caused by lentivirus, a member of retrovirus family that is known as Human Immunodeficiency Virus (HIV)[1]. It is a condition where human immune system progressively fails, which invites various other diseases, infection and even cancer to fight. This virus attacks most vital cells in immune system; helper T cells (CD4+ T cells), macrophages and dendritic cells, because it cannot replicate on it own and needs these cells to replicate [2]. HIV works towards decreasing CD4+ T cells in three ways: First, by killing the CD4+ T cells directly, second, by increase apoptosis rate and third by indirect mechanism where CD8 cytotoxic lymphocytes (it recognizes infected cells and try to eradicate them) kill CD4+ T cells because they are infected by lentivirus. CD4+ T cells level decreases to such an extent where no self-immunity is left in human body.

HIV is classified into two categories; HIV-1 and HIV-2, HIV-1 is a the common HIV which is easily transmitted and is more virulent and infective while HIV-2 is less transmitted and mostly found in West Africa part only.

According to UNAID statistics, in 2010 there were around 1.8 million people died due to AIDS and around 34 million people are still living with AIDS. It is becoming so severe that it is necessary to have good treatment for it, although there are 25 drugs in market for AIDS but each one of them have some or the other side effects in them which cannot be ignored.

1 LIFE CYCLE OF HIV
There are series of stages in HIV life cycle, they are: Binding and fusion, Reserve transcription, integration, assembly and budding. Each step is explained in brief as following. Stepwise stages have been demonstrated in figure 1.

1.1 Binding and fusion: HIV enters into cell membrane via absorption of glycoprotein, gp120. This gp120 binds with CD4 antigen, which are present on peripheral of the helper T cell and macrophages. The interaction is stabilized by chemokine receptors, which are also present along with CD4 antigen [3] [4]. This interaction leads to conformation change in gp120. All this causes conformational change in gp41, which expose hydrophobic region of the host cell. Membrane of virus now interacts with the hydrophobic region of host cell that allows nucleocaspid to penetrate into cytoplasm of host cell. Nucleocaspid contains a viral protein vpr, which promote entry to nuclear pore.

1.2 Reverse transcription: Soon after viral capsid enters inside the cell, an enzyme name reverse transcriptase cleaves single stranded RNA genome from viral and copies into complementary DNA (cDNA) molecule. Reverse transcriptase has ribonuclease activity that serve as potential target for antiretroviral therapy, which is discussed below in potential targets section. cDNA and its complement forms double stranded viral DNA, which then enters into cell nucleus.

1.3 Integration: The process of viral DNA entering into cell nucleus is done by another enzyme name integrase. For virus to remain active some transcription factors needs to be present i.e. NF-κB (NF kappa B)[5], which upreagulates in...
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