HIV and Ebola Viruses: HIV Mechanisms, Lifecycle, and Therapeutic Targets | MIT OpenCourseWare

This MIT OpenCourseWare lecture uses HIV as a powerful exemplar to illustrate virology concepts from virus structure to life cycle. It explains how HIV targets CD4+ T cells using the GP120 and GP41 envelope proteins, and how co-receptors CCR5 and CXCR4 enable entry, followed by fusion and uncoating. The talk then traces the genome and replication steps, highlighting reverse transcriptase, integrase, and protease as critical enzymes and drug targets. It discusses four main therapeutic targets—fusion/entry, reverse transcription, integration, and protease maturation—and describes the evolution of combination antiretroviral therapy, viral reservoirs in the genome, and the rationale for lifelong treatment. The lecture also touches on TB co-infection, drug resistance, and the public health resources that support HIV research and treatment.

Overview

The lecture from MIT OpenCourseWare centers HIV as a retrovirus to teach core virology and therapeutic concepts. It covers HIV's envelope organization, receptor targeting, and the life cycle that enables lifelong infection if untreated.

HIV Structure and Entry

The virus is enveloped and presents GP120 and GP41 on its surface. The GP120 glycoprotein binds the CD4 receptor on T cells and, with the CCR5 or CXCR4 co-receptor, mediates membrane fusion through GP41. This entry step is a critical juncture for infection and a target for antiviral strategies.

Genome, Replication, and Maturation

Inside the virion, single-stranded positive RNA is reverse transcribed by reverse transcriptase into DNA. Integrase then inserts the viral DNA into the host genome, establishing a lifelong reservoir. Viral RNA is transcribed into mRNA, which is translated into polyproteins and subsequently cleaved by the viral protease into functional proteins. This maturation process is essential for producing infectious virions and is a key drug target.

Antiretroviral Targets and Therapies

The talk outlines four primary therapeutic targets: fusion/entry, reverse transcription, integration, and protease activity. Early inhibitors included nucleoside analogs like azidothymidine (AZT), a prodrug activated by cellular kinases to block DNA synthesis. Integrase inhibitors and protease inhibitors evolved to improve potency and reduce side effects, enabling combination therapies that suppress viral replication and reduce resistance.

Clinical and Public Health Context

The lecture emphasizes co-infection with TB due to immunodeficiency, the concept of viral reservoirs in the host genome that necessitate lifelong treatment, and the importance of public health resources (such as the NIH and NIAID) for research funding and information dissemination.

Outlook

While HIV draws most of the focus, the session also mentions Ebola and the broader context of viral pathogenesis, vaccine development, and therapeutic strategies. The talk concludes with notes on course logistics and upcoming activities, including interactive review and assessments.