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Mini Review - Research and Reports in Immunology (2023) Volume 6, Issue 4
The key players: CD4+ t cell determinants of HIV infection
Letebrhan Weldemhret *
Department of Medical Microbiology, Mekelle University, Mekelle, Ethiopia.
- *Corresponding Author:
- Letebrhan Weldemhret
Department of Medical Microbiology
Mekelle University
Mekelle, Ethiopia.
E-mail: Letebrhan@gmail.com
Received:28-Jul-2023, Manuscript No. AARRI-23-108395; Editor assigned: 30-Jul-2023,PreQC No. AARRI-23-108395 (PQ); Reviewed:14-Aug-2023,QC No. AARRI-23-108395; Revised:18-Aug-2023, Manuscript No. AARRI-23-108395(R); Published:25-Aug-2023,DOI:10.35841/aarrgs-6.4.157
Citation: Weldemhret L. The key players: CD4+ t cell determinants of HIV infection. Res Rep Immunol. 2022; 6(4):157
Introduction
Human Immunodeficiency Virus (HIV) continues to be one of the most significant global health challenges, with over 38 million people living with the virus worldwide. Despite tremendous progress in understanding the virus and developing antiretroviral therapy (ART), a cure remains elusive. HIV primarily targets the immune system's CD4+ T cells, leading to their depletion and subsequent immunodeficiency. This article aims to explore the critical determinants of CD4+ T cell infection by HIV, shedding light on the complex interplay between the virus and the immune system.CD4+ T cells play a central role in orchestrating the immune response. These specialized white blood cells serve as mediators and coordinators, guiding other immune cells in their battle against pathogens. Upon recognizing antigens presented by antigen-presenting cells (APCs), CD4+ T cells differentiate into various subsets, such as Th1, Th2, Th17, and Tregs, each tailored to address specific types of infections.[1,2].
The human immunodeficiency virus enters the body through exposure to infected bodily fluids, primarily blood, sexual contact, or mother-to-child transmission during childbirth or breastfeeding. HIV's target cells are CD4+ T cells, along with other immune cells expressing CD4 receptors, like macrophages and dendritic cells. The viral entry is initiated through a two-step process: binding of the viral envelope glycoprotein, gp120, to the CD4 receptor, followed by interaction with a co-receptor, typically CCR5 or CXCR4. The variability of HIV strains and their preference for co-receptor usage contribute to the diverse clinical presentations and disease progression rates observed in infected individuals. R5-tropic viruses predominantly use CCR5 co-receptor, while X4-tropic viruses preferentially utilize CXCR4. Some strains can also use both CCR5 and CXCR4 co-receptors, known as dual-tropic or mixed-tropic viruses. The selective pressure exerted by the immune system and antiretroviral drugs can lead to the emergence of different co-receptor usage patterns, influencing the rate of disease progression [3,4].
HIV's ability to evade the immune system is a formidable challenge in developing effective treatments and vaccines. The virus employs several strategies to escape CD4+ T cell-mediated immune responses: High Mutation Rate: HIV has a high mutation rate due to the error-prone nature of its reverse transcriptase enzyme. This leads to the generation of diverse viral variants (quasispecies) within an infected individual, making it difficult for the immune system to mount a targeted response. Latency and Reservoir Formation: HIV can establish latent infections in long-lived memory CD4+ T cells, which are not effectively targeted by the immune system or antiretroviral drugs. These reservoirs serve as a continuous source of virus, even during effective ART. Downregulation of MHC Class I: HIV downregulates the major histocompatibility complex class I (MHC-I) molecules on infected cells, reducing their visibility to cytotoxic CD8+ T cells, which would otherwise recognize and destroy infected cells. T Cell Exhaustion: Chronic exposure to HIV antigens leads to the functional exhaustion of HIV-specific CD4+ T cells. These cells lose their effector functions and become less capable of controlling the infection. Immune Activation and Inflammation: HIV induces chronic immune activation and inflammation, leading to increased turnover of CD4+ T cells and creating an environment conducive to viral replication. The human leukocyte antigen (HLA) system plays a critical role in the immune response against HIV. HLA molecules present viral antigens to CD4+ T cells, initiating an immune response. HLA alleles are highly polymorphic, leading to individual variations in the ability to present HIV antigens. Certain HLA alleles, such as HLA-B27 and HLA-B57, have been associated with slower disease progression, as they can effectively present conserved viral epitopes to the immune system [5].
Conclusion
Understanding the complex interplay between HIV and CD4+ T cells is crucial for developing effective strategies to combat the virus. The relentless assault on the immune system by HIV highlights the need for innovative approaches to enhance the immune response, such as therapeutic vaccines and immunotherapies. Additionally, uncovering the intricacies of co-receptor usage and viral latency could pave the way for novel antiretroviral therapies that specifically target hidden reservoirs. As research in immunology and virology progresses, we move closer to the ultimate goal of finding a cure for HIV and improving the quality of life for millions of people living with the virus.
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