HIV Life Cycle and Inherited Co‐Receptors

Abstract

Human immunodeficiency virus (HIV) is a Lentivirus of the family Retroviridae , members of which cause a number of neurological and immunological diseases in humans and animals. HIV is the causative agent of the acquired immune deficiency syndrome. The disease is caused by virus‐mediated depletion of CD4+ T lymphocytes, preferentially CCR5‐positive memory T cells. Most of these cells localise to mucosal tissue, in particular gut mucosa, and disruption of the gut mucosal barrier is an early feature of HIV infection that determines the pathogenesis of the disease. More than 20 years of intensive studies identified the molecular mechanisms underlying viral replication and disease pathogenesis and provided the foundation for development of antiviral therapeutics and vaccine. This article provides a brief overview of the HIV life cycle and focuses on receptors that determine viral binding and entry into the target cells. Key Concepts: Virus entry into target cell is initiated by interaction between gp120 and cell receptors. HIV preferentially targets memory CD4+ T cells that localise to mucosal lymphoid tissue, in particular the gut mucosa. HIV replication includes a number of distinct steps: virus–cell fusion and entry, uncoating, reverse transcription and formation of the pre‐integration complex (PIC), PIC nuclear entry and integration, transcription and translation of proviral DNA, viral assembly and release of nascent virions and maturation and formation of infectious virions. To infect a target cell, virus needs to counteract the activity of multiple cellular antiviral factors (APOBEC3, SAMHD1, tetherin), most of which activated by interferon. HIV accessory proteins have evolved to perform this function. Receptors determine not only the first step of HIV interaction with the target cell, but also regulate post‐entry events in viral replication. Characterisation of the molecular mechanisms underlying HIV replication and interaction with the target cells provides an opportunity to develop anti‐HIV therapeutics and vaccine.