Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA–viral peptide interaction as the major factor modulating durable control of HIV infection.

BACKGROUND Multiple health problems have been reported in survivors of Ebola virus disease (EVD). Attribution of these problems to the disease without a control group for analysis is difficult. METHODS We enrolled a cohort of EVD survivors and their close contacts and prospectively collected data on symptoms, physical examination findings, and laboratory results. A subset of participants underwent ophthalmologic examinations. Persistence of Ebola virus (EBOV) RNA in semen samples from survivors was determined. RESULTS A total of 966 EBOV antibody–positive survivors and 2350 antibody-negative close contacts (controls) were enrolled, and 90% of these participants were followed for 12 months. At enrollment (median time to baseline visit, 358 days after symptom onset), six symptoms were reported significantly more often among survivors than among controls: urinary frequency (14.7% vs. 3.4%), headache (47.6% vs. 35.6%), fatigue (18.4% vs. 6.3%), muscle pain (23.1% vs. 10.1%), memory loss (29.2% vs. 4.8%), and joint pain (47.5% vs. 17.5%). On examination, more survivors than controls had abnormal abdominal, chest, neurologic, and musculoskeletal findings and uveitis. Other than uveitis (prevalence at enrollment, 26.4% vs. 12.1%; at year 1, 33.3% vs. 15.4%), the prevalence of these conditions declined during follow-up in both groups. The incidence of most symptoms, neurologic findings, and uveitis was greater among survivors than among controls. EBOV RNA was detected in semen samples from 30% of the survivors tested, with a maximum time from illness to detection of 40 months. CONCLUSIONS A relatively high burden of symptoms was seen in all participants, but certain symptoms and examination findings were more common among survivors. With the exception of uveitis, these conditions declined in prevalence during follow-up in both groups. Viral RNA in semen persisted for a maximum of 40 months.

There is an approximately linear proportionality between autosomal DNA content and observed breakpoint number, suggesting that subsets of autosomes can be used to estimate accurately the overall genomic frequency of misrejoined breakpoints contingent upon a carefully selected subset. However, this conclusion may not apply to the sex chromosomes. The results also support the influence of chromatin organization and/or preferential DNA repair/misrejoining on the distribution of induced breakpoints. However, these effects are not sufficient at a global level to dismiss the value of cytogenetic analysis using a genome subset for biodosimetry.

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