Gene silencing in HIV-1 latency by polycomb repressive group

<p>Abstract</p> <p>Background</p> <p>The persistence of latently Human immunodeficiency virus-1 (HIV-1) infected cellular reservoirs in resting CD4⁺T cells is a major obstacle to HIV-1 eradication. The detailed mechanism of HIV-1 latency remains unclear. We investigated histones and their post-translational modification associated with HIV-1 latency in novel HIV-1 latently infected cell lines established previously, NCHA cells.</p> <p>Methods</p> <p>To examine histones and their modification linked with HIV-1 latency, the expression profiles for core histone proteins and histone deacetylases (HDACs) in NCHA cells were characterized by RT-PCR, ELISA, and western blot. The levels of histone acetylation and methylation at histone H3 Lys⁹(H3K9) and Lys²⁷(H3K27) in HIV-1 latently infected cells were analyzed by western blot and chromatin immunoprecipitation-sequencing (ChIP-seq).</p> <p>Results</p> <p>The expression levels for four core histone proteins (H2A, H2B, H3 and H4) and HDACs (HDAC1-8) in NCHA cells were not significantly different from those in their parental cells. Histone H3K9 and H3K27 acetylations in NCHA cells showed no difference in parental and NCHA cells, whereas the levels of di- and tri-methylation were increased in NCHA cells. The expression of EED which is a component of polycomb repressive complex 2 (PRC2), and BMI1 and RING2 which are constituents of PRC1, were upregulated in NCHA cells. In addition, more ubiquitylation at histone H2A was detected in NCHA cells.</p> <p>Conclusions</p> <p>Our results suggest that tri-methylation of histone H3K27 and H2A ubiquitylation via polycomb group protein may play a crucial role in epigenetic silencing accounting for HIV-1 latency in NCHA cells.</p

Increasing late diagnosis in HIV infection in South Korea: 2000-2007

<p>Abstract</p> <p>Background</p> <p>The number of Koreans diagnosed with human immunodeficiency virus (HIV) infections is increasing annually; however, CD4+ T-cell counts at diagnosis have decreased. The purpose of the present study was to identify clinical and epidemiologic associations with low CD4+ T-cell counts at the time of HIV diagnosis in a Korean population.</p> <p>Methods</p> <p>Data from 2,299 HIV-infected individuals with initial CD4+ T-cell counts measured within 6 months of HIV diagnosis and reason for HIV testing were recorded and measured from 2000 to 2007. Data were selected from the database of the Korea Centers for Disease Control and Prevention. Late diagnosis was defined by CD4+ T-cell counts <200 cells/mm³. Reasons for HIV testing were analyzed using logistic regression including epidemiologic variables.</p> <p>Results</p> <p>A total of 858 individuals (37.3%) were included in the late diagnosis group. Individuals with a late diagnosis were older, exposed through heterosexual contact, and demonstrated clinical manifestations of acquired immunodeficiency syndrome (AIDS). The primary reason for HIV testing was a routine health check-up (41%) followed by clinical manifestations (31%) of AIDS. The proportion of individuals with a late diagnosis was higher in individuals tested due to clinical symptoms in public health centers (adjusted odds ratio [AOR], 17.3; 95% CI, 1.7-175) and hospitals (AOR, 4.9; 95% CI, 3.4-7.2) compared to general health check-up. Late diagnosis annually increased in individuals diagnosed by voluntary testing both in public health centers (PHCs, P = 0.017) and in hospitals (P = 0.063). Routine testing due to risky behaviors resulted in earlier detection than testing secondary to health check-ups, although this difference was not statistically significant (AOR, 0.7; P = 0.187). Individuals identified as part of hospital health check-ups more frequently had a late diagnosis (P = 0.001)</p> <p>Conclusions</p> <p>HIV infection was primarily detected by voluntary testing with identification in PHCs and by testing due to clinical symptoms in hospitals. However, early detection was not influenced by either voluntary testing or general health check-up. It is important to encourage voluntary testing for early detection to decrease the prevalence of HIV infection and AIDS progression.</p

Prevalence of human papillomavirus infection and genotype distribution among high-risk Korean women for prospecting the strategy of vaccine development

We investigated the prevalence of human papillomavirus (HPV) infection and the distribution of high-risk HPV genotypes among 2,308 high-risk Korean women to predict how much the current prophylactic HPV vaccines might affect the prevention of cervical cancer in Korea. HPV DNA was detected in 939 women (40.7%) but only one-third of women were positive for HPV-16 and/or HPV-18, the genotypes used for developing the HPV vaccines. Thus, the development of area-specific HPV vaccines based on dominant HPV genotypes in our country is needed for preventing HPV infection and the development of premalignant lesions in the cervix of Korean women

Monotherapy versus combination therapy of statin and renin–angiotensin system inhibitor in ST-segment elevation myocardial infarction

Background: The beneficial effects of statin and renin–angiotensin system inhibitor (RASI) are well-known. In this retrospective cohort study,  2-year clinical outcomes were compared between monotherapy and combination therapy with statin and RASI in ST-segment elevation myocardial infarction (STEMI) patients after stent implantation. Methods: A total of 17,414 STEMI patients were enrolled and divided into the three groups (group A: 2448 patients, statin alone; group B: 2431 patients, RASI alone; and group C: 12,535 patients, both statin and RASI). The principal clinical endpoint was the occurrence of major adverse cardiac events (MACEs) defined as all-cause death, recurrent myocardial infarction, and any repeat revascularization. Results: After adjustment, the cumulative incidences of MACEs in group A (adjusted hazard ratio [aHR] 1.337; 95% confidence interval [CI] 1.064–1.679; p = 0.013) and in group B (aHR 1.375; 95% CI 1.149–1.646; p = 0.001) were significantly higher than in group C. The cumulative incidence of all-cause death in group A was significantly higher than that in group C (aHR 1.539; 95% CI 1.014–2.336; p = 0.043). The cumulative incidences of any repeat revascularization (aHR 1.317; 95% CI 1.031–1.681; p = 0.028), target lesion vascularization, and target vessel vascularization in group B were significantly higher than in group C. Conclusions: A Statin and RASI combination therapy significantly reduced the cumulative incidence of MACEs compared with a monotherapy of these drugs. Moreover, the combination therapy showed a reduced all-cause death rate compared with statin monotherapy, and a decreased repeat revascularization rate compared with RASI monotherapy