Expansion of a novel endogenous retrovirus throughout the pericentromeres of modern humans

Abstract Background Approximately 8% of the human genome consists of sequences of retroviral origin, a result of ancestral infections of the germ line over millions of years of evolution. The most recent of these infections is attributed to members of the human endogenous retrovirus type-K (HERV-K) (HML-2) family. We recently reported that a previously undetected, large group of HERV-K (HML-2) proviruses, which are descendants of the ancestral K111 infection, are spread throughout human centromeres. Results Studying the genomes of certain cell lines and the DNA of healthy individuals that seemingly lack K111, we discover new HERV-K (HML-2) members hidden in pericentromeres of several human chromosomes. All are related through a common ancestor, termed K222, which is a virus that infected the germ line approximately 25 million years ago. K222 exists as a single copy in the genomes of baboons and high order primates, but not New World monkeys, suggesting that progenitor K222 infected the primate germ line after the split between New and Old World monkeys. K222 exists in modern humans at multiple loci spread across the pericentromeres of nine chromosomes, indicating it was amplified during the evolution of modern humans. Conclusions Copying of K222 may have occurred through recombination of the pericentromeres of different chromosomes during human evolution. Evidence of recombination between K111 and K222 suggests that these retroviral sequences have been templates for frequent cross-over events during the process of centromere recombination in humans.http://deepblue.lib.umich.edu/bitstream/2027.42/111301/1/13059_2015_Article_641.pd

Estimation of HIV-1 incidence among five focal populations in Dehong, Yunnan: a hard hit area along a major drug trafficking route

<p>Abstract</p> <p>Background</p> <p>Since 1989 when the first 146 HIV positives in China were identified, Dehong Prefecture had been one of the areas hardest-hit by HIV in China. The local and national governments have put substantial financial resources into tackling the HIV epidemic in Dehong from 2004. The objective of this study was to track dynamic changes in HIV-1 prevalence and incidence among five focal populations in Dehong and to assess the impact of HIV prevention and control efforts.</p> <p>Methods</p> <p>Consecutive cross-sectional surveys conducted in five focal populations between 2004 and 2008. Specimens seropositive for HIV were tested with the BED IgG capture enzyme immunoassay to identify recent seroconversions (median, 155 days) using normalized optical density of 0.8 and adjustments.</p> <p>Results</p> <p>From 2004 to 2008, estimated annual HIV incidence among injecting drug users (IDUs) decreased significantly [from 15.0% (95% CI = 11.4%-18.5%) in 2004 to 4.3% (95% CI = 2.4%-6.2%) in 2008; trend test P < 0.0001]. The incidence among other focal populations, such as HIV discordant couples (varying from 5.5% to 4.7%), female sex workers (varying from 1.4% to 1.3%), pregnant women (0.1%), and pre-marital couples (0.2 to 0.1%) remained stable. Overall, the proportion of recent HIV-1 infections was higher among females than males (P < 0.0001).</p> <p>Conclusions</p> <p>The HIV epidemic in Dehong continued to expand during a five-year period but at a slowing rate among IDUs, and HIV incidence remains high among IDUs and discordant couples. Intensive prevention measures should target sub-groups at highest risk to further slow the epidemic and control the migration of HIV to other areas of China, and multivariate analysis is needed to explore which measures are more effective for different populations.</p

Antiretroviral therapy reduces HIV transmission in discordant couples in rural Yunnan, China.

BACKGROUND: Although HIV treatment as prevention (TasP) via early antiretroviral therapy (ART) has proven to reduce transmissions among HIV-serodiscordant couples, its full implementation in developing countries remains a challenge. In this study, we determine whether China's current HIV treatment program prevents new HIV infections among discordant couples in rural China. METHODS: A prospective, longitudinal cohort study was conducted from June 2009 to March 2011, in rural Yunnan. A total of 1,618 HIV-discordant couples were eligible, 1,101 were enrolled, and 813 were followed for an average of 1.4 person-years (PY). Routine ART was prescribed to HIV-positive spouses according to eligibility (CD4<350 cells/µl). Seroconversion was used to determine HIV incidence. RESULTS: A total of 17 seroconversions were documented within 1,127 PY of follow-up, for an overall incidence of 1.5 per 100 PY. Epidemiological and genetic evidence confirmed that all 17 seroconverters were infected via marital secondary sexual transmission. Having an ART-experienced HIV-positive partner was associated with a lower rate of seroconvertion compared with having an ART-naïve HIV-positive partner (0.8 per 100 PY vs. 2.4 per 100 PY, HR = 0.34, 95%CI = 0.12-0.97, p = 0.0436). While we found that ART successfully suppressed plasma viral load to <400 copies/ml in the majority of cases (85.0% vs. 19.5%, p<0.0001 at baseline), we did document five seroconversions among ART-experienced subgroup. CONCLUSIONS: ART is associated with a 66% reduction in HIV incidence among discordant couples in our sample, demonstrating the effectiveness of China's HIV treatment program at preventing new infections, and providing support for earlier ART initiation and TasP implementation in this region

Stratification analysis of consistent condom use in the past 12 months at follow-up survey among study of HIV discordant couples in rural Yunnan, China, 2009–2011.

<p>PY: Person-years.</p>*<p>Only those already on ART at baseline or started ART before the midpoint were considered to be receiving ART for the purposes of stratification analyses.</p

Characteristics of the five individuals who seroconverted despite their HIV-positive spouse receiving ART among study of HIV discordant couples in rural Yunnan, China, 2009–2011.

<p>LDL: lower detection limit, which for this study was 50 copies/ml.</p>*<p>All 5 seroconverters answered no to commercial sex, non-commercial sex, and injection drug use questions for both lifetime and most recent 12-month time periods, thus this data was not included in the table.</p>†<p>Frequency of sex variable related to sex with spouses within the past 12 months.</p>‡<p>Consistent condom use variable related to sex with spouses within the past 12 months.</p>§<p>All HIV-positive spouses of the 5 seroconverters were on ART already at baseline.</p

Comparison of characteristics of HIV-negative and HIV-positive partners at baseline and follow up relative to whether the HIV-positive partner (index case) was on ART or naïve to ART among study of HIV discordant couples in rural Yunnan, China, 2009–2011.

<p>IQR: Inter-quartile range.</p>*<p>A total of 82 HIV-positive partners (index cases) began ART during the follow-up period. At baseline, these individuals were included in the “Naïve to ART” category and at follow-up, they were included in the “On ART” category.</p