Apparent Founder Effect during the Early Years of the San Francisco HIV Type 1 Epidemic (1978–1979)

Abstract

HIV-1 envelope sequence variants were RT-PCR amplified from serum samples cryopreserved in San Francisco in 1978-1979. The HIV-1 subtype B env V3-V5 sequences from four homosexual men clustered phylogenetically, with a median nucleotide distance of 2.8%, reflecting a recent common origin. These early U.S. HIV-1 env variants mapped close to the phylogenetic root of the subtype B tree while env variants collected in the United States throughout the 1980s and 1990s showed, on average, increasing genetic diversity and divergence from the subtype B consensus sequence. These results indicate that the majority of HIV-1 currently circulating in the United States may be descended from an initial introduction and rapid spread during the mid- to late 1970s of subtype B viruses with limited variability (i.e., a founder effect). As expected from the starburst-shaped phylogeny of HIV-1 subtype B, contemporary U.S. strains were, on average, more closely related at the nucleic acid and amino acid levels to the earlier 1978-1979 env variants than to each other. The growing levels of HIV-1 genetic diversity, one of multiple obstacles in designing a protective vaccine, may therefore be mitigated by using epidemic founding variants as antigenic strains for protection against contemporary strains.

Sequencing-Based Detection of Low-Frequency Human Immunodeficiency Virus Type 1 Drug-Resistant Mutants by an RNA/DNA Heteroduplex Generator-Tracking Assay

“…As expected from prior studies of DNA/DNA heteroduplexes (18,19,21), mobility retardation generally increased with greater divergence between the reannealed target DNA and RNA probe strands. The higher level of divergence between PCPXM and the subtype consensus is more typical of currently circulating HIV-1 strains than the lower level of divergence seen with the pNL4-3 and RF strains, both collected early in the subtype B epidemic (26,32,51). Different pNL4-3-derived mutants showed minor but reproducible mobility differences, except for V82I and I84V, whose mobilities were undistinguishable, and L10F, whose mobility was identical to that of pNL4-3.…”

Human Immunodeficiency Virus Type 1 Superinfection Was Not Detected following 215 Years of Injection Drug User Exposure

“…Conversely, a highly drugresistant superinfecting strain may have a selective advantage over resident wild-type variants in patients on antiviral drug therapy. Last, a large and growing level of viral genetic diversity, both within HIV-1 subtype B (19,34,44) and worldwide (21), and increasing circulation of different subtypes and their recombinants may all lead to increasing frequencies of superinfection.…”

U.S. Human Immunodeficiency Virus Type 1 Epidemic: Date of Origin, Population History, and Characterization of Early Strains

“…Although non-B subtype infections have been identified in the United States in recent years (2,12), most of these infections have occurred in African-born individuals (38). The large proportion of subtype B infections presumably reflects founder effects of early strains in North America (7,25). In the United States, the AIDS epidemic was first recognized in June 1981 with the report of an outbreak of Pneumocystis pneumonia among homosexual men (3).…”