RAB11FIP5 Expression and Altered Natural Killer Cell Function Are Associated with Induction of HIV Broadly Neutralizing Antibody Responses

HIV-1 broadly neutralizing antibodies (bnAbs) are difficult to induce with vaccines but are generated in ∼50% of HIV-1-infected individuals. Understanding the molecular mechanisms of host control of bnAb induction is critical to vaccine design. Here, we performed a transcriptome analysis of blood mononuclear cells from 47 HIV-1-infected individuals who made bnAbs and 46 HIV-1-infected individuals who did not and identified in bnAb individuals upregulation of RAB11FIP5, encoding a Rab effector protein associated with recycling endosomes. Natural killer (NK) cells had the highest differential expression of RAB11FIP5, which was associated with greater dysregulation of NK cell subsets in bnAb subjects. NK cells from bnAb individuals had a more adaptive/dysfunctional phenotype and exhibited impaired degranulation and cytokine production that correlated with RAB11FIP5 transcript levels. Moreover, RAB11FIP5 overexpression modulated the function of NK cells. These data suggest that NK cells and Rab11 recycling endosomal transport are involved in regulation of HIV-1 bnAb development. Generation of broadly neutralizing antibodies against HIV-1 in humans is linked to the expression of a specific recycling endosome-associated effector in natural killer cells

Food-web regulation by a planktivore: exploring the generality of the trophic cascade hypothesis

The trophic cascade hypothesis currently being tested in north temperate systems may not apply to open-water communities in lower latitude U.S. reservoirs. These reservoir communities differ dramatically from northern lakes in that an open-water omnivore, gizzard shad (Dorosoma cepedianum), often occurs in abundance. Neither controlled by fish predators (owing to high fecundity and low vulnerability) nor by their zooplankton prey (following the midsummer zooplankton decline, gizzard shad consume detritus and phytoplankton), gizzard shad regulate community composition rather than being regulated by top-down or bottom-up forces. In experiments across a range of spatial scales (enclosures, 1-9 m2; ponds, 4-5 ha; and reservoirs, 50-100 ha), we evaluated the generality of the trophic cascade hypothesis by assessing its conceptual strength in reservoir food webs. We reviewed the role of gizzard shad in controlling zooplankton populations and hence recruitment of bluegill, Lepomis macrochirus (via exploitative competition for zooplankton), and largemouth bass, Micropterus salmoides (by reducing their bluegill prey). Reservoir fish communities, owing to the presence of gizzard shad, appear to be regulated more by complex weblike interactions among species than by the more chainlike interactions characteristic of the trophic cascade.Funding for this project was provided by National Science Foundation (NSF) grants DEB9107173 and DEB9407859 to R.A.S. and NSF grants DEB9108986 and DEB9410323 to D.R.D