HIV Biology: Detailed Insight into Virion Structural Organization and Its Pathogenesis

Human immunodeficiency virus is a member of the Retroviridae family, primarily infecting human CD4+ T cells, which leads to gradual depletion in the CD4+ T cell count. When the T cell count comes below a critical level (200 cells/mm3), this condition is called as acquired immunodeficiency syndrome (AIDS). At this stage, the risk of infection with several other opportunistic pathogens increases, which ultimately leads to the death of the infected individual, if remains untreated. It was first reported by the US Centers for Disease Control and Prevention (CDC) in the middle of 1981, which became a global pandemic within a few years. Around 38.0 million people globally (according to UNAIDS) and 2.3 million people in India (according to NACO) were living with HIV in 2019. HIV is classified into two types, HIV-1 and HIV-2. HIV-1 is more infective compared to HIV-2 and has spread globally. HIV-1 comprises two copies of single-stranded RNA molecule of about 9.8 Kb long surrounded by a capsid protein layer. HIV-1 genome encodes about 15 viral proteins. Due to the limited number of viral proteins, HIV-1 hijacks host cellular machinery and exploits a large number of host proteins to complete its life cycle successfully. Over the last four decades, extensive research has been done to combat HIV infection, but we still do not have a potential therapeutic regimen that can cure HIV completely. Currently prescribed drug combination, highly active antiretroviral therapy (HAART), which targets the key enzymes of the virus, can keep the viral load below detectable level, but does not eliminate the virus completely from the infected individual and has some drawbacks like the development of drug resistance, drug toxicity, etc. Thus, it has become crucial to identify and characterize cellular factors which are involved in establishing or restricting HIV-1 replication and pathogenesis. Several genome-wide screening studies have identified such cellular proteins associated with the HIV-1 replication process and control it either positively or negatively and are thus called proviral or antiviral factors. The use of some of these host factors as potential targets for HIV-1 infection is actively being pursued. Despite intense studies, host-pathogen interaction still remains to be clearly understood. Therefore, it remains an important area of research with direct association with the knowledge of infection transmission, pathogenic mechanisms, vaccine design, and molecular targets for therapeutic development.