X-Linked RNA-Binding Motif Protein Modulates HIV-1 Infection of CD4+ T Cells by Maintaining the Trimethylation of Histone H3 Lysine 9 at the Downstream Region of the 5' Long Terminal Repeat of HIV Proviral DNA.

Reversible repression of HIV-1 5' long terminal repeat (5'-LTR)-mediated transcription represents the main mechanism for HIV-1 to maintain latency. Identification of host factors that modulate LTR activity and viral latency may help develop new antiretroviral therapies. The heterogeneous nuclear ribonucleoproteins (hnRNPs) are known to regulate gene expression and possess multiple physiological functions. hnRNP family members have recently been identified as the sensors for viral nucleic acids to induce antiviral responses, highlighting the crucial roles of hnRNPs in regulating viral infection. A member of the hnRNP family, X-linked RNA-binding motif protein (RBMX), has been identified in this study as a novel HIV-1 restriction factor that modulates HIV-1 5'-LTR-driven transcription of viral genome in CD4+ T cells. Mechanistically, RBMX binds to HIV-1 proviral DNA at the LTR downstream region and maintains the repressive trimethylation of histone H3 lysine 9 (H3K9me3), leading to a blockage of the recruitment of the positive transcription factor phosphorylated RNA polymerase II (RNA pol II) and consequential impediment of transcription elongation. This RBMX-mediated modulation of HIV-1 transcription maintains viral latency by inhibiting viral reactivation from an integrated proviral DNA. Our findings provide a new understanding of how host factors modulate HIV-1 infection and latency and suggest a potential new target for the development of HIV-1 therapies.IMPORTANCE HIV-1 latency featuring silence of transcription from HIV-1 proviral DNA represents a major obstacle for HIV-1 eradication. Reversible repression of HIV-1 5'-LTR-mediated transcription represents the main mechanism for HIV-1 to maintain latency. The 5'-LTR-driven HIV gene transcription can be modulated by multiple host factors and mechanisms. The hnRNPs are known to regulate gene expression. A member of the hnRNP family, RBMX, has been identified in this study as a novel HIV-1 restriction factor that modulates HIV-1 5'-LTR-driven transcription of viral genome in CD4+ T cells and maintains viral latency. These findings provide a new understanding of how host factors modulate HIV-1 infection and latency and suggest a potential new target for the development of HIV-1 therapies.

[The effects of different occluder selection on cardiac remodeling post transcatheter closure in patients with secundum atrial septal defect].

OBJECTIVE: To evaluate the effects on cardiac remodeling post transcatheter closure by Amplatzer septal occluder selected by oval circumference formula in patients with atrial septal defect (ASD). METHODS: A total of 146 patients with ASD (68 males,mean 33.5 years) treated by transcatheter closure with the Amplatzer occluder were enrolled in this study. The diameter of defects was corrected with the oval circumference formula (group A, 73 cases) or by echocardiography (group B, 73 cases). Cardiac remodeling was assessed by transthoracic echocardiography (TTE) before the procedure, 3 days, 3 months and 6 months after ASD closure. RESULTS: The mean ASD diameter was similar between the two groups [(20.16 +/- 4.98) mm vs. (21.36 +/- 5.69) mm, P > 0.05] and the mean diameter of the selected occluder of group A was significantly smaller than that in group B [(21.95 +/- 6.78) mm vs. (25.85 +/- 6.75) mm, P < 0.05]. Procedural success rate was identical between the two groups (97.3%) and the defects were completely occluded and there was no residual shunt during the 6 months follow up period, there were also no complications during and after the procedure. The lateral diameter of right atrial (RALD), the diastolic diameter of right ventricle (RVDD), RALD/LALD, RVDD/LVDD and pulmonary diameter (PD) were significantly decreased while the lateral diameter of left atrial (LALD) and left ventricle (LVDD) were significantly increased post ASD closure in both groups. At 6 months follow up, RALD decreased by (18.63 +/- 10.59)% in group A versus (10.14 +/- 6.59)% in group B, LALD increased by (13.42 +/- 8.38)% in group A versus (9.28 +/- 4.95)% in group B and RALD/LALD ratio decreased by (26.35 +/- 11.24)% in group A versus (13.98 +/- 8.96)% in groups B (all P < 0.05). CONCLUSION: ASD occluder selection based on the oval circumferen ce formula is superior to that made by echocardiography in terms of more favorable cardiac remodeling post ASD closure.