There exists a unique group of persons who are able to durably control HIV in the absence of therapy. The mechanisms of control in these persons remain poorly defined. In this study, we examined CD8 ؉ T-cell responses in blood and rectal mucosa from 17 "elite controllers" (viral load < 75 copies/mL), 11 "viremic controllers" (75-2000 copies/mL), 14 noncontrollers (> 10 000 copies/mL), and 10 antiretroviral-treated persons (< 75 copies/mL). Production of interferon-␥, interleukin-

Microbiomes are vast communities of microbes and viruses that populate all natural ecosystems. Viruses have been considered the most variable component of microbiomes, as supported by virome surveys and examples of high genomic mosaicism. However, recent evidence suggests that the human gut virome is remarkably stable compared to other environments. Here we investigate the origin, evolution, and epidemiology of crAssphage, a widespread human gut virus. Through a global collaboratory, we obtained DNA sequences of crAssphage from over one-third of the world's countries, and showed that its phylogeography is locally clustered within countries, cities, and individuals. We also found colinear crAssphage-like genomes in both Old-World and New-World primates, challenging genomic mosaicism and suggesting that the association of crAssphage with primates may be millions of years old. We conclude that crAssphage is a benign globetrotter virus that may have co-evolved with the human lineage and an integral part of the normal human gut virome.

Global climate change includes rising temperatures and increased pCO2 concentrations in the ocean, with potential deleterious impacts on marine organisms. In this case study we conducted a four-week climate change incubation experiment, and tested the independent and combined effects of increased temperature and partial pressure of carbon dioxide (pCO2), on the microbiomes of a foundation species, the giant kelp Macrocystis pyrifera, and the surrounding water column. The water and kelp microbiome responded differently to each of the climate stressors. In the water microbiome, each condition caused an increase in a distinct microbial order, whereas the kelp microbiome exhibited a reduction in the dominant kelp-associated order, Alteromondales. The water column microbiomes were most disrupted by elevated pCO2, with a 7.3 fold increase in Rhizobiales. The kelp microbiome was most influenced by elevated temperature and elevated temperature in combination with elevated pCO2. Kelp growth was negatively associated with elevated temperature, and the kelp microbiome showed a 5.3 fold increase Flavobacteriales and a 2.2 fold increase alginate degrading enzymes and sulfated polysaccharides. In contrast, kelp growth was positively associated with the combination of high temperature and high pCO2 ‘future conditions’, with a 12.5 fold increase in Planctomycetales and 4.8 fold increase in Rhodobacteriales. Therefore, the water and kelp microbiomes acted as distinct communities, where the kelp was stabilizing the microbiome under changing pCO2 conditions, but lost control at high temperature. Under future conditions, a new equilibrium between the kelp and the microbiome was potentially reached, where the kelp grew rapidly and the commensal microbes responded to an increase in mucus production.

A small percentage of human immunodeficiency virus (HIV)-infected individuals, termed elite controllers, are able to spontaneously control HIV replication in blood. As the gastrointestinal mucosa is an important site of HIV transmission and replication as well as CD4؉ T-cell depletion, it is important to understand the nature of the immune responses occurring in this compartment. Although the role of the HIV-specific CD8؉ T-cell responses in mucosal tissues has been described, few studies have investigated the role of mucosal HIV-specific CD4 ؉ T cells. In this study, we assessed HIV-specific CD4 ؉ T-cell responses in the rectal mucosa of 28 "controllers" (viral load [VL] of <2,000 copies/ml), 14 "noncontrollers" (VL of >10,000 copies/ml), and 10 individuals on highly active antiretroviral therapy (HAART) (VL of <75 copies/ml). Controllers had highermagnitude Gag-specific mucosal CD4؉ T-cell responses than individuals on HAART (P < 0. 05), as measured by their ability to produce gamma interferon (IFN-␥), interleukin-2 (IL-2), tumor necrosis factor alpha (TNF-␣), and macrophage inflammatory protein 1␤ (MIP-1␤). The frequency of polyfunctional mucosal CD4 ؉ T cells was also higher in controllers than in noncontrollers or individuals on HAART (P < 0.05). Controllers with the strongest HIV-specific CD4؉ T-cell responses possessed class II HLA alleles, HLA-DRB1*13 and/or HLA-DQB1*06, previously associated with a nonprogression phenotype. Strikingly, individuals with both HLA-DRB1*13 and HLA-DQB1*06 had highly polyfunctional mucosal CD4 ؉ T cells compared to individuals with HLA-DQB1*06 alone or other class II alleles. The frequency of polyfunctional CD4 ؉ T cells in rectal mucosa positively correlated with the magnitude of the mucosal CD8 ؉ T-cell response (Spearman's r ‫؍‬ 0.43, P ‫؍‬ 0.005), suggesting that increased CD4 ؉ T-cell "help" may be important in maintaining strong CD8 ؉ T-cell responses in the gut of HIV controllers.

Background: The vertebrate clade diverged into Chondrichthyes (sharks, rays, and chimeras) and Osteichthyes fishes (bony fishes) approximately 420 mya, with each group accumulating vast anatomical and physiological differences, including skin properties. The skin of Chondrichthyes fishes is covered in dermal denticles, whereas Osteichthyes fishes are covered in scales and are mucous rich. The divergence time among these two fish groups is hypothesized to result in predictable variation among symbionts. Here, using shotgun metagenomics, we test if patterns of diversity in the skin surface microbiome across the two fish clades match predictions made by phylosymbiosis theory. We hypothesize (1) the skin microbiome will be host and clade-specific, (2) evolutionary difference in elasmobranch and teleost will correspond with a concomitant increase in host-microbiome dissimilarity, and (3) the skin structure of the two groups will affect the taxonomic and functional composition of the microbiomes. Results: We show that the taxonomic and functional composition of the microbiomes is host-specific. Teleost fish had lower average microbiome within clade similarity compared to among clade comparison, but their composition is not different among clade in a null based model. Elasmobranch's average similarity within clade was not different than across clade and not different in a null based model of comparison. In the comparison of host distance with microbiome distance, we found that the taxonomic composition of the microbiome was related to host distance for the elasmobranchs, but not the teleost fishes. In comparison, the gene function composition was not related to the host-organism distance for elasmobranchs but was negatively correlated with host distance for teleost fishes.