Contrasting antibody responses to intrasubtype superinfection with CRF02_AG

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.

Near full genome characterization of HIV‐1 unique recombinant forms in Cameroon reveals dominant CRF02_AG and F2 recombination patterns

“…The characterization of circulating HIV‐1 M strains in Africa is incomplete, particularly in West‐Central Africa, where the diversity of subtypes is exceptionally high. A crucial genetic feature of HIV is its recombination‐prone nature leading to the emergence of intra‐ and inter‐subtype recombinants in dually infected individuals . Currently, there are at least 98 CRFs , and numerous URFs identified, composed of pure and other recombinant subtypes including under‐sampled parental lineages that cannot be reasonably classified within the established HIV‐1 M subtypes .…”

Immunological and virological characteristics of human immunodeficiency virus type 1 superinfection: implications in vaccine design

“…If intervals are short (e.g., weeks) during follow-up, superinfection can be accurately and timely detected [21,40]. If intervals are long (e.g., months or years), superinfection may be missed due to the rapid recombination between primary and superinfected viruses [35,52–55], which can lead to the misclassification of the superinfection as monoinfection with divergent viruses. Therefore, the incidence or prevalence of superinfection can be underestimated in low-frequency sampling cohorts and might be the reason for the nondetection of superinfection in some studies [34,35,37,56,57].…”

“…Recombination between primary infection viruses and superinfection viruses can be rapidly detected, and recombinants could quickly replace the parental viruses soon after superinfection under the selection of T cell or nAb pressure [35,52–55]. Thus, the rapid recombination between superinfection and primary infection viruses may allow recombinants to quickly escape the preexisting immune responses and be an important cause for the second virus to successfully establish superinfection.…”

“…This study demonstrated that strong and sustained cellular and humoral immune responses as well as low replicating viruses are associated with viral control in the superinfected LTNP elite controller. However, broad neutralization activities were not detected in some superinfected cases [52]. It seems that the timing of superinfection and genetic characteristics (diversity, length variation, potential glycosylation site, and others) of superinfection viruses might contribute to development of broad and potent nAb responses [52].…”

“…However, broad neutralization activities were not detected in some superinfected cases [52]. It seems that the timing of superinfection and genetic characteristics (diversity, length variation, potential glycosylation site, and others) of superinfection viruses might contribute to development of broad and potent nAb responses [52]. These observations indicate that multiple immunogen variants may be needed to induce cross-reactive immune responses to diverse heterologous viruses.…”