Viral evolution and escape during acute HIV-1 infection

Abstract

The extensive genetic diversity of human immunodeficiency virus type 1 (HIV-1) presents a significant barrier to the development of an effective and durable HIV vaccine. This variability not only makes it difficult to identify the targets against which immune responses should be directed, but it also confers on the virus the capacity for rapid escape from effective immune responses. Here, we describe recent investigations of the genetic diversity of HIV-1 at transmission and of the evolution of the virus as it adapts to the host immune environment during the acute phase of HIV-1 infection. These studies increase our understanding of the virology of the earliest stages of HIV-1 infection and provide critical insights into the mechanisms underlying viral replication and immune control of diverse HIV-1 strains. Such knowledge will inform the design of smarter, more effective vaccines capable of inducing immune control of HIV-1.

Figure 1. Differential founder virus replication and immune escape from dominant CD8+ T cell responses combine to influence the HIV-1 set-point viral load and clinical course

The differential replication of wild type (solid line) and attenuated (dashed line) founder viruses results in different levels of peak viremia and long-term control of HIV-1. The impact of dominant CD8+ T cell responses (red cells) on the viral population is determined by the relative rate of escape in the targeted epitopes (grey diamonds) which ranges from immediate escape (top set-point line) as the result of the escape mutations being transmitted in the founder virus to never (bottom set-point line) as the result of high escape-associated fitness costs and low viral replication. The differential founder virus replication and dominant CD8+ T cell response effectiveness result in poor control of acute HIV-1 replication and high set-point viral load (red set-point line), normal control and set-point (green lines), and protective control and low to undetectable set-point (blue set-point lines).