Bottlenecks in HIV-1 transmission: insights from the study of founder viruses

Key Points Approximately 80% of HIV-1 heterosexual transmission events are established from a single transmitted/founder (T/F) virus. During transmission, multiple bottlenecks reduce the viral population from the large, genetically variable population in the blood of a chronically infected donor to a single T/F virus in the newly infected recipient. Recent evidence suggests that transmission of a single T/F virus results from both stochastic bottlenecks that restrict transmission of all viruses (for example, nonspecific barrier functions) and selective bottlenecks that favour transmission of viruses with specific phenotypes. Understanding the bottlenecks that restrict transmission may inform targets for prevention strategies. For example, antiretrovirals can be used to suppress the viral population in infected individuals and prevent them from sexually transmitting HIV-1 (that is, 'treatment as prevention'). HIV-1 infection typically results from the transmission of a single viral variant, the transmitted/founder (T/F) virus. In this Review, Joseph and colleagues discuss how studying these T/F viruses contributes to a better understanding of HIV-1 transmission and affects prevention strategies. HIV-1 infection typically results from the transmission of a single viral variant, the transmitted/founder (T/F) virus. Studies of these HIV-1 variants provide critical information about the transmission bottlenecks and the selective pressures acting on the virus in the transmission fluid and in the recipient tissues. These studies reveal that T/F virus phenotypes are shaped by stochastic and selective forces that restrict transmission and may be targets for prevention strategies. In this Review, we highlight how studies of T/F viruses contribute to a better understanding of the biology of HIV-1 transmission and discuss how these findings affect HIV-1 prevention strategies.