Brandon F Keele1. 1. AIDS and Cancer Virus Program, SAIC-Frederick, Inc, National Cancer Institute-Frederick, Frederick, Maryland 21702, USA. keelebf@mail.nih.gov
Abstract
PURPOSE OF REVIEW: Improvements in sequencing approaches and robust mathematical modeling have dramatically increased information on viral genetics during acute infection with HIV and simian immunodeficiency virus, providing unprecedented insight into viral transmission and viral/immune interactions. RECENT FINDINGS: Overall viral genetic diversity is reduced significantly during mucosal transmission. Remarkably, in the vast majority of sexual transmissions, this diversity is reduced to a single viral variant that establishes the initial productive clinical infection. By identifying and enumerating transmitted/founder viruses, researchers can begin to define the characteristics that are necessary and sufficient for successful viral replication within a new host. SUMMARY: Acute HIV infection is a critical window of opportunity for vaccine and therapeutic intervention. New sequencing technologies and mathematical modeling of transmission and early evolution have provided a clearer understanding of the number of founder viruses that establish infection, the rapid generation of diversity in these viruses and the subsequent evasion of host immunity. The information gained by identifying transmitted viruses, monitoring the initial host responses to these viruses and then identifying mechanisms of viral escape could provide better strategies for vaccine development, preexposure prophylaxis, microbicides, or other therapeutic interventions.
PURPOSE OF REVIEW: Improvements in sequencing approaches and robust mathematical modeling have dramatically increased information on viral genetics during acute infection with HIV and simian immunodeficiency virus, providing unprecedented insight into viral transmission and viral/immune interactions. RECENT FINDINGS: Overall viral genetic diversity is reduced significantly during mucosal transmission. Remarkably, in the vast majority of sexual transmissions, this diversity is reduced to a single viral variant that establishes the initial productive clinical infection. By identifying and enumerating transmitted/founder viruses, researchers can begin to define the characteristics that are necessary and sufficient for successful viral replication within a new host. SUMMARY: Acute HIV infection is a critical window of opportunity for vaccine and therapeutic intervention. New sequencing technologies and mathematical modeling of transmission and early evolution have provided a clearer understanding of the number of founder viruses that establish infection, the rapid generation of diversity in these viruses and the subsequent evasion of host immunity. The information gained by identifying transmitted viruses, monitoring the initial host responses to these viruses and then identifying mechanisms of viral escape could provide better strategies for vaccine development, preexposure prophylaxis, microbicides, or other therapeutic interventions.
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