Abstract
HIV superinfection describes the sequential infection of an individual with two or more unrelated HIV strains. Intersubtype superinfection has been shown to cause a broader and more potent heterologous neutralizing antibody response when compared to singly infected controls, yet the effects of intrasubtype superinfection remain controversial. Longitudinal samples were analyzed phylogenetically for pol and env regions using Next-Generation Sequencing and envelope cloning. The impact of CRF02_AG intrasubtype superinfection was assessed for heterologous neutralization and antibody binding responses. We compared two cases of CRF02_AG intrasubtype superinfection that revealed complete replacement of the initial virus by superinfecting CRF02_AG variants with signs of recombination. NYU6564, who became superinfected at an early time point, exhibited greater changes in antibody binding profiles and generated a more potent neutralizing antibody response post-superinfection compared to NYU6501. In contrast, superinfection occurred at a later time point in NYU6501 with strains harboring significantly longer V1V2 regions with no observable changes in neutralization patterns. Here we show that CRF02_AG intrasubtype superinfection can induce a cross-subtype neutralizing antibody response, and our data suggest timing and/or superinfecting viral envelope characteristics as contributing factors. These results highlight differential outcomes in intrasubtype superinfection and provide the first insight into cases with CRF02_AG, the fourth most prevalent HIV-1 strain worldwide.
Highlights
HIV-1 superinfection is characterized by the sequential infection of an individual with two or more genetically unrelated HIV-1 strains and provides a unique opportunity to study the adaptive immune response to challenges with multiple antigens [1, 2]
We studied 6 plasma samples collected from 2002–2014 spanning at least 10 years including samples pre and post-SI (Fig 1)
SI occurred in a window of 7 years that included a period of short term antiretroviral therapy (ART) during pregnancy
Summary
HIV-1 superinfection is characterized by the sequential infection of an individual with two or more genetically unrelated HIV-1 strains and provides a unique opportunity to study the adaptive immune response to challenges with multiple antigens [1, 2]. The secondary challenge of the immune system by a SI event can boost a strong immune response, as observed for various cases of SI with a different subtype (intersubtype SI) [11, 12]. The increased breadth and potency of the heterologous neutralizing antibody (nAb) response has been attributed to the elevated antigenic stimulation with diverse strains [13, 14]. SI within the same subtype (intrasubtype SI), which generates an inherent lower genetic diversity, creates varied results, ranging from strongly enhanced to unchanged immune responses when compared to singly infected controls [12, 15,16,17,18,19]. Comparing cases of intrasubtype SI with contrasting Ab responses allows for the study of critical parameters for the design of vaccine immunogens that generate a strong Ab response
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