HIV tropism

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Mapping SHIV infection in the body%2C 2018 - Wellcome Photography Prize 2019 (bottom right%2C cropped)

HIV tropism refers to the specific cellular preference that the Human Immunodeficiency Virus (HIV) exhibits when infecting the human immune system. This tropism is crucial for understanding the pathogenesis of HIV, as well as for developing targeted antiretroviral therapy strategies. HIV primarily targets CD4+ T cells, which play a critical role in the immune response, but it can also infect other cell types such as macrophages and dendritic cells. The mechanism of entry into these cells is determined by the virus's use of specific coreceptors, which, along with the CD4 receptor, facilitate viral entry.

Coreceptors and Tropism

The two main coreceptors used by HIV are CCR5 and CXCR4. Based on the coreceptor usage, HIV strains can be classified into three main types: R5-tropic, X4-tropic, and dual-tropic.

• R5-tropic strains use the CCR5 coreceptor and are most commonly involved in the initial stages of HIV infection.
• X4-tropic strains use the CXCR4 coreceptor and are more often associated with the later stages of infection and a more rapid progression to AIDS.
• Dual-tropic strains can use both CCR5 and CXCR4 coreceptors and have the capability to infect a broader range of cell types.

Clinical Significance

The determination of HIV tropism is of significant clinical importance, especially when considering treatment options. Maraviroc, an antiretroviral drug, specifically targets CCR5-tropic HIV strains by blocking the CCR5 receptor, thereby preventing the virus from entering cells. Therefore, testing for HIV tropism is crucial before initiating treatment with maraviroc to ensure its efficacy.

Testing for HIV Tropism

Testing methods for HIV tropism include phenotypic assays, which directly measure the ability of the virus to use a specific coreceptor, and genotypic assays, which analyze the genetic sequence of the virus to predict coreceptor usage. Genotypic assays are more commonly used due to their lower cost and faster turnaround times.

Implications for Vaccine Development

Understanding HIV tropism is also vital for HIV vaccine development. A vaccine that could elicit a robust immune response against HIV, regardless of its coreceptor usage, would be a significant breakthrough in the fight against HIV/AIDS.

Conclusion

HIV tropism plays a fundamental role in the pathogenesis, treatment, and potential prevention of HIV/AIDS. Ongoing research into the mechanisms of HIV entry and the development of new therapies targeting different aspects of this process continues to be a critical area of study in the field of virology and infectious diseases.