Impact of pre-adapted HIV transmission.

Human leukocyte antigen class I (HLA)-restricted CD8(+) T lymphocyte (CTL) responses are crucial to HIV-1 control. Although HIV can evade these responses, the longer-term impact of viral escape mutants remains unclear, as these variants can also reduce intrinsic viral fitness. To address this, we here developed a metric to determine the degree of HIV adaptation to an HLA profile.

HIV control is mediated in part by CD8+ T-cell targeting of specific epitopes.

Unlabelled: We investigated the hypothesis that the correlation between the class I HLA types of an individual and whether that individual spontaneously controls HIV-1 is mediated by the targeting of specific epitopes by CD8(+) T cells. By measuring gamma interferon enzyme-linked immunosorbent spot (ELISPOT) assay responses to a panel of 257 optimally defined epitopes in 341 untreated HIV-infected persons, including persons who spontaneously control viremia, we found that the correlation between HLA types and control is mediated by the targeting of specific epitopes. Moreover, we performed a graphical model-based analysis that suggested that the targeting of specific epitopes is a cause of such control--that is, some epitopes are protective rather than merely associated with control--and identified eight epitopes that are significantly protective.

HIV transmission. Selection bias at the heterosexual HIV-1 transmission bottleneck.

Heterosexual transmission of HIV-1 typically results in one genetic variant establishing systemic infection. We compared, for 137 linked transmission pairs, the amino acid sequences encoded by non-envelope genes of viruses in both partners and demonstrate a selection bias for transmission of residues that are predicted to confer increased in vivo fitness on viruses in the newly infected, immunologically naïve recipient. Although tempered by transmission risk factors, such as donor viral load, genital inflammation, and recipient gender, this selection bias provides an overall transmission advantage for viral quasispecies that are dominated by viruses with high in vivo fitness.

Correlates of protective cellular immunity revealed by analysis of population-level immune escape pathways in HIV-1.

HLA class I-associated polymorphisms identified at the population level mark viral sites under immune pressure by individual HLA alleles. As such, analysis of their distribution, frequency, location, statistical strength, sequence conservation, and other properties offers a unique perspective from which to identify correlates of protective cellular immunity. We analyzed HLA-associated HIV-1 subtype B polymorphisms in 1,888 treatment-naïve, chronically infected individuals using phylogenetically informed methods and identified characteristics of HLA-associated immune pressures that differentiate protective and nonprotective alleles.

SCOPE: a web server for practical de novo motif discovery.

SCOPE is a novel parameter-free method for the de novo identification of potential regulatory motifs in sets of coordinately regulated genes. The SCOPE algorithm combines the output of three component algorithms, each designed to identify a particular class of motifs. Using an ensemble learning approach, SCOPE identifies the best candidate motifs from its component algorithms.

SPACER: identification of cis-regulatory elements with non-contiguous critical residues.

Motivation: Many transcription factors bind to sites that are long and loosely related to each other. De novo identification of such motifs is computationally challenging. In this article, we propose a novel semi-greedy algorithm over the space of all IUPAC degenerate strings to identify the most over-represented highly degenerate motifs.