Identifying and characterizing recently transmitted viruses

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.

Figure 1. Indentifying the transmitted virus using single genome amplification and mathematical modeling

Infection with a single variant is determined by generating sequences during acute infection and comparing all sequences to themselves. In panel A, of the 21 sequences shown in the tree (left) and in the highlighter alignment (center) over half (62%) are identical to themselves and identical to the consensus over the entire env gene. The remaining sequences differ from this consensus sequence by one (33%) or two (5%) mutations. The differences between all sequences are compared to a Poisson distribution and deviations are identified by a goodness of fit test. When two sequences are transmitted (B), variant 1 (black) can be distinguished from variant 2 (grey) and the consensus of each lineage represents a unique transmitted/founder viral sequences. When all sequences from both lineages are compared, the Poisson distribution does not fit, but is restored when each lineage is analyzed independently.