Objective To investigate the susceptibilities to and consequences of HIV-1 dual infection (DI). Design We compared clinical, virologic, and immunologic factors between participants who were dually infected with HIV-1 subtype B, and monoinfected (MI) controls who were matched by ongoing HIV risk factor. Methods The viral load and CD4 progressions of dually and singly infected participant groups were compared with linear mixed-effects models, and individual dynamics before and after superinfection were assessed with a structural change test (Chow test). Recombination breakpoint analysis (GARD), HLA frequency analysis, and cytotoxic T-lymphocyte (CTL) epitope mapping were also performed (HIV LANL Database). Results The viral loads of DI participants increased more over 3 years of follow-up than the viral loads of MI controls, while CD4 progressions of the two groups did not differ. Viral escape from CTL responses following superinfection was observed in two participants whose superinfecting strain completely replaced the initial strain. This pattern was not seen among participants whose superinfecting virus persisted in a recombinant form with the initial virus or was only detected transiently. Several HLA types were overrepresented in DI participants as compared to MI controls. Conclusions These results identify potential factors for DI susceptibility and further define its clinical consequences.

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To better understand the innate immune response to infection, we tracked gene expression in the duodenal mucosa of 11 Bangladeshi adults with cholera, using biopsy specimens obtained immediately after rehydration and 30 and 180 days later. We identified differentially expressed genes and performed an analysis to predict differentially regulated pathways and upstream regulators. During acute cholera, there was a broad increase in the expression of genes associated with innate immunity, including activation of the NF-κB, mitogen-activated protein kinase (MAPK), and Toll-like receptor (TLR)-mediated signaling pathways, which, unexpectedly, persisted even 30 days after infection. Focusing on early differences in gene expression, we identified 37 genes that were differentially expressed on days 2 and 30 across the 11 participants. These genes included the endosomal Toll-like receptor gene, which was expressed in lamina propria cells. Underscoring a potential role for endosomal TLR-mediated signaling , our pathway analysis found that interferon regulatory factor 7 and beta 1 and alpha 2 interferons were among the top upstream regulators activated during cholera. Among the innate immune effectors, we found that the gene for DUOX2, an NADPH oxidase involved in the maintenance of intestinal homeostasis, was upregulated in intestinal epithelial cells during cholera. Notably, the observed increases in and expression were also modeled when Caco-2 or THP-1 cells, respectively, were stimulated with live but not with heat-killed organisms or cholera toxin alone. These previously unidentified features of the innate immune response to extend our understanding of the mucosal immune signaling pathways and effectors activated following cholera.