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

Abstract

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.

Resistance to type 1 interferons is a major determinant of HIV-1 transmission fitness

“…S2A). Unlike in some previous studies (8), there was no evidence of compartmentalization of plasma and genital secretion isolates from donors CH492 and CH742 (SI Appendix, Fig. S3 and Table S2B).…”

“…In 2015, ∼2 million individuals were newly infected with HIV-1, the great majority of whom acquired the virus by sexual routes (1). Although a number of factors, such as high donor viral loads, genital inflammation, altered mucosal microbiota, and recipient gender, are known to increase the infection risk (2-4), virus transmission across intact mucosal surfaces is inherently inefficient, with only a small fraction (less than 1%) of unprotected sexual exposures leading to productive infection (5)(6)(7)(8). This inefficiency is exemplified by a stringent population bottleneck, in which only one or a limited number of variants from the diverse quasispecies of the transmitting donor establish the new infection (9).…”

Clonal expansion of genome-intact HIV-1 in functionally polarized Th1 CD4+ T cells

“…PBMC samples were collected according to protocols approved by the respective Institutional Review Boards. Study geneous populations of founder viruses (31). Given that the small sequence variations that we observed between individual intact proviral sequences from patients with acute infection were randomly distributed over the entire genome, these minor sequence differences are likely to result from the error rate of viral reverse transcriptase occurring during infection of distinct cells.…”

Transmitted/Founder HIV-1 Subtype C Viruses Show Distinctive Signature Patterns in Vif, Vpr, and Vpu That Are Under Subsequent Immune Pressure During Early Infection

“…However, limited data exist on amino acid signature patterns within viral proteins, particularly in HIV-1 subtype C t/f viruses. 20 Moreover, limited data exist on the timing of escape mutations in HIV-1 subtype C accessory genes. 16,18 In this study, we reconstructed the t/f viruses derived from the earliest available sequences from 17 individuals with acute/ early HIV-1C infection.…”

“…All available subtype C sequences fitting these criteria were included in our analysis. The majority of sequences included (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27) South Africa (*50%), followed by Botswana (*25%) and others (Supplementary Table S1; Supplementary Data are available online at www.liebertpub.com/aid). A maximum likelihood phylogeny inferred from our combined early and chronic HIV-1 vif sequences was created to confirm that the acute/early sequences are generally interspersed among the chronic ones ( Supplementary Fig.…”