| Publication Abstract Display | | Type: Published Manuscript | | Title: Dynamics of viral evolution and neutralizing antibody response after HIV-1 superinfection. | | Authors: Chaillon A, Wagner G A, Hepler NL, Little SJ, Kosakovsky Pond SL, Caballero G, Pacold ME, Phung P, Wrin T, Richman DD, Wertheim JO, Smith DM | | Year: 2013 | | Publication: Journal of Virology | | Volume: 87 Issue: 23 Pages: 12737-44 | | Abstract:Investigating the incidence and prevalence of HIV-1 superinfection is challenging due to the complex dynamics of two infecting strains. The superinfecting strain can replace the initial strain, be transiently expressed, or persist along with the initial strain in distinct or in recombined forms. Various selective pressures influence these alternative scenarios in different HIV-1 coding regions. We hypothesized that the potency of the neutralizing antibody (NAb) response to autologous viruses would modulate viral dynamics in env following superinfection in a limited set of superinfection cases. HIV-1 env pyrosequencing data were generated from blood plasma collected from 7 individuals with evidence of superinfection. Viral variants within each patient were screened for recombination and viral dynamics evaluated using nucleotide diversity. NAb responses to autologous viruses were evaluated before and after superinfection. In 4 individuals, the superinfecting strain replaced the original strain. In 2 individuals, both initial and superinfecting strains continued to co-circulate. In the final individual, the surviving lineage was the product of inter-strain recombination. NAb responses to autologous viruses were weak or absent for 6 of the 7 recently infected individuals at the time of and shortly following superinfection that were detected within the first 2 years of HIV-1 infection. These 6 individuals had detectable on-going viral replication of distinct superinfecting virus in the env coding region. In the remaining case, there was an early and strong autologous NAb response, which was associated with extensive recombination in env between initial and superinfecting strains. This extensive recombination made superinfection more difficult to identify and may explain why the detection of superinfection has typically been associated with low autologous NAb titers. |
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