Identifying the mechanisms of natural control of HIV-1 infection could lead to novel approaches to prevent or cure HIV infection. Several studies have associated natural control of HIV-1 infection with IgG antibodies against HIV-1 Gag proteins (e.g. p24) and/or production of IgG2 antibodies against HIV-1 proteins. These antibodies likely exert their effect by activating anti-viral effector cell responses rather than virus neutralization. We hypothesized that an opsonophagocytic IgG antibody response against HIV-1 p24 that activates plasmacytoid dendritic cells (pDCs) through FcγRIIa would be associated with control of HIV and that this would be enhanced by antibody isotype diversification. Using the Gen2.2 pDC cell line, we demonstrated that pDC-reactive opsonophagocytic IgG antibody responses against HIV-1 p24 were higher in HIV controllers (HIV RNA <2000 copies/mL) than non-controllers (HIV RNA >10,000 copies/mL) particularly in controllers with low but detectable viremia (HIV RNA 75–2000 copies/mL). Opsonophagocytic antibody responses correlated with plasma levels of IgG1 and IgG2 anti-HIV-1 p24 and notably, correlated inversely with plasma HIV RNA levels in viremic HIV patients. Phagocytosis of these antibodies was mediated via FcγRIIa. Isotype diversification (towards IgG2) was greatest in HIV controllers and depletion of IgG2 from immunoglobulin preparations indicated that IgG2 antibodies to HIV-1 p24 do not enhance phagocytosis, suggesting that they enhance other aspects of antibody function, such as antigen opsonization. Our findings emulate those for pDC-reactive opsonophagocytic antibody responses against coxsackie, picorna and influenza viruses and demonstrate a previously undefined immune correlate of HIV-1 control that may be relevant to HIV vaccine development.

Control of early HIV-1 infection was associated with an increase in HIV-1 p24-specific PROAb responses, which was mediated by HIV-1 p24-specific IgG1 antibodies. These findings provide further evidence that antibodies to HIV core proteins may contribute to control of HIV-1 infection.

The Western Australian camaenid genera Plectorhagada and Strepsitaurus have morphological similarities and mutually exclusive ranges near Cape Range. Sequences of ctyochrome c oxidase subunit I (COI) and 16S mitochondrial DNA (mtDNA) genes confirmed that the two genera are genetically close sister clades. Targeted sampling showed that Strepsitaurus, which is confined to Cape Range, lies within a hole in the distribution of the more broadly distributed Plectorhagada that occurs on the coastal strip surrounding Cape Range. Species of the two genera meet at the transition between the rocky Cape Range and the sandier coastal areas, providing a rare example of the close replacement of genera. Within each genus, mtDNA sequences confirmed the monophyly and genetic distinctness of species, with few exceptions that show the need for additional work, and with the addition of three new species in the Cape Range area. As is typical of Australian camaenids, distributions of congeneric species are mutually exclusive, but in some cases close proximity is associated with contrasting habitats, such as gorge endemics versus the species on top of Cape Range. In sympatry, Strepsitaurus rugus (Cotton, 1951) and Strepsitaurus williami Solem, 1997 are separated by microhabitat. These local associations with habitat indicate that ecological differences, and not simply allopatric divergence, contribute to the lack of sympatry between closely related Australian camaenids.

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