What is the cellular tropism of HIV? Does it change during the course of an infection? Which cellular receptors confer the preference for infection of certain cell-types? What effect does the choice of host cell have on the pathogenesis of HIV?
HIV has been the most extensively studied and researched virus in history. Part of the knowledge you should attain from this course is a thorough understanding of the basics of HIV infection, pathogenesis and treatment. To this end, I have come up with a series of questions/topics which should help you, along with the text reading, develop a basic knowledge foundation for HIV. Each student should become an expert on one of the questions/topics and then post a PowerPoint or Jing presentation (preferred) explaining the topic to the rest of the class. After posting your essay/presentation you should then ask one question of one of your classmates.Objectives
• You should develop an understanding of the features of HIV that enable it to be such a massive global health problem and is difficult to treat both pharmacologically and prevent with a vaccine.
• You should understand the role of the major viral accessory proteins in an infection such as Vif, VPR, VPU, Nef and REV.
• You should be able to describe the modes of transmission of HIV (sexual contact, IV drug use…etc) and which are most common in various parts of the world.
• You should understand the course of an HIV infection including the features of the acute, asymptomatic and symptomatic phases and the status of the immune system at each phase.
• You should be able to explain why HIV-infected individuals are more susceptible to opportunistic infections.
• You should be able to enumerate the cells that HIV infects and how it causes immune dysfunction.
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The cell type, infecting which the HIV replicates is scientifically referred to as HIV tropism. The major cellular targets which are often marked by HIV in-vivo are the macrophages, T-cells and dendritic cells. [1]This selection of tropism is principally resulted based upon the type of cell-surface receptors, which is required for HIV to get attached with. The attachment further use to govern the entry of virus into host biochemical cellular system. Research till now have demonstrated that in general, two such different receptors viz. CD4+ T cell and a co-receptor are much essential and crucial for HIV to proceed for infection. The most commonly and popularly known co-receptor is the chemokine receptor CCR5. Another co-receptor, which is very commonly used in HIV variant is CXCR4-G protein-coupled 7-transmembrane protein.
Theory behind the entry of HIV into cell: HIV is known to interact with CD4 and co-receptor (either CCR5 or CXCR4) to initiate its entry into the cell. The spike like projecting material over the viral surface, envelope glycoprotein, which are comprised of trimer of approximately three gp120 and three gp41 molecules. [3] A structural change is induced upon binding of CD4 to gp120 and is an important event necessary for exposing the binding site for the co-receptors, thereby exposing the hydrophobic domains. Once the co-receptor gets bound, further more structural changes get induced.
