Evidence of HIV-1 adaptation to host HLA alleles following chimp-to-human transmission

<p>Abstract</p> <p>Background</p> <p>The cytotoxic T-lymphocyte immune response is important in controlling HIV-1 replication in infected humans. In this immune pathway, viral peptides within infected cells are presented to T-lymphocytes by the polymorphic human leukocyte antigens (HLA). HLA alleles exert selective pressure on the peptide regions and immune escape mutations that occur at some of the targeted sites can enable the virus to adapt to the infected host. The pattern of ongoing immune escape and reversion associated with several human HLA alleles has been studied extensively. Such mutations revert upon transmission to a host without the HLA allele because the escape mutation incurs a fitness cost. However, to-date there has been little attempt to study permanent loss of CTL epitopes due to escape mutations without an effect on fitness.</p> <p>Results</p> <p>Here, we set out to determine the extent of adaptation of HIV-1 to three well-characterized HLA alleles during the initial exposure of the virus to the human cytotoxic immune responses following transmission from chimpanzee. We generated a chimpanzee consensus sequence to approximate the virus sequence that was initially transmitted to the human host and used a method based on peptide binding affinity to HLA crystal structures to predict peptides that were potentially targeted by the HLA alleles on this sequence. Next, we used codon-based phylogenetic models to quantify the average selective pressure that acted on these regions during the period immediately following the zoonosis event, corresponding to the branch of the phylogenetic tree leading to the common ancestor of all of the HIV-1 sequences. Evidence for adaptive evolution during this period was observed at regions recognised by HLA A*6801 and A*0201, both of which are common in African populations. No evidence of adaptive evolution was observed at sites targeted by HLA-B*2705, which is a rare allele in African populations.</p> <p>Conclusion</p> <p>Our results suggest that the ancestral HIV-1 virus experienced a period of positive selective pressure due to immune responses associated with HLA alleles that were common in the infected human population. We propose that this resulted in permanent escape from immune responses targeting unconstrained regions of the virus.</p

Biophysical Factors Affecting the Distribution of Demersal Fish around the Head of a Submarine Canyon Off the Bonney Coast, South Australia

We sampled the demersal fish community of the Bonney Canyon, South Australia at depths (100–1,500 m) and locations that are poorly known. Seventy-eight species of demersal fish were obtained from 12 depth-stratified trawls along, and to either side, of the central canyon axis. Distributional patterns in species richness and biomass were highly correlated. Three fish assemblage groupings, characterised by small suites of species with narrow depth distributions, were identified on the shelf, upper slope and mid slope. The assemblage groupings were largely explained by depth (ρw = 0.78). Compared to the depth gradient, canyon-related effects are weak or occur at spatial or temporal scales not sampled in this study. A conceptual physical model displayed features consistent with the depth zonational patterns in fish, and also indicated that canyon upwelling can occur. The depth zonation of the fish assemblage was associated with the depth distribution of water masses in the area. Notably, the mid-slope community (1,000 m) coincided with a layer of Antarctic Intermediate Water, the upper slope community (500 m) resided within the core of the Flinders Current, and the shelf community was located in a well-mixed layer of surface water (<450 m depth)

Discordant Impact of HLA on Viral Replicative Capacity and Disease Progression in Pediatric and Adult HIV Infection

HLA class I polymorphism has a major influence on adult HIV disease progression. An important mechanism mediating this effect is the impact on viral replicative capacity (VRC) of the escape mutations selected in response to HLA-restricted CD8+ T-cell responses. Factors that contribute to slow progression in pediatric HIV infection are less well understood. We here investigate the relationship between VRC and disease progression in pediatric infection, and the effect of HLA on VRC and on disease outcome in adult and pediatric infection. Studying a South African cohort of >350 ART-naïve, HIV-infected children and their mothers, we first observed that pediatric disease progression is significantly correlated with VRC. As expected, VRCs in mother-child pairs were strongly correlated (p = 0.004). The impact of the protective HLA alleles, HLA-B*57, HLA-B*58:01 and HLA-B*81:01, resulted in significantly lower VRCs in adults (p<0.0001), but not in children. Similarly, in adults, but not in children, VRCs were significantly higher in subjects expressing the disease-susceptible alleles HLA-B*18:01/45:01/58:02 (p = 0.007). Irrespective of the subject, VRCs were strongly correlated with the number of Gag CD8+ T-cell escape mutants driven by HLA-B*57/58:01/81:01 present in each virus (p = 0.0002). In contrast to the impact of VRC common to progression in adults and children, the HLA effects on disease outcome, that are substantial in adults, are small and statistically insignificant in infected children. These data further highlight the important role that VRC plays both in adult and pediatric progression, and demonstrate that HLA-independent factors, yet to be fully defined, are predominantly responsible for pediatric non-progression

DNA barcoding of rays from the South China Sea

Fishery management on elasmobranchs is gaining attention in recent years due to their economic value and the key ecological role played by them in their natural habitat. Many species of elasmobranch, especially rays, exhibit overlapping morphological similarities and hence difficult to identify to their species level. As an accurate identification is key for developing a framework for fishery management, we used a molecular approach to identify ray fishes sampled from South China Sea. We used Cytochrome oxidase subunit I (COI) sequencing (~652 bp) to cross-examine field identification of ray fishes. A total of 10 species belonging to 3 families were successfully sequenced/identified from 29 PCR products. BLAST/BOLD analysis was performed and inter- and intra-species genetic distance was calculated. Due to overlapping morphological characters and morphocryptic nature, their accurate field identification is challenging. We also addressed problems in species-level delimitation of ray fishes due to the paucity of information in DNA databanks besides unresolved taxonomic status of available dataset. We further addressed management and action plan for sustainable management of elasmobranch fishery in Malaysia