Activity of superior interferon α against HIV-1 in severe combined immunodeficient mice reconstituted with human peripheral blood leukocytes / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Interferon (IFN) can inhibit human immunodeficiency virus type 1 (HIV-1) replication in vitro and in clinic. However, IFN therapy for HIV infection was limited by its moderate antiviral efficacy and its frequent adverse effects. In the present study we evaluated the anti-HIV efficacy of a novel synthesized superior interferon α (sIFNα).</p><p><b>METHODS</b>We performed in vitro experiments with HIV-1 IIIB infected MT4 cells, and evaluated in vivo anti-HIV efficacy of sIFNα in severe combined immunodeficient (SCID) mice reconstituted with human peripheral blood leukocytes (hu-PBL-SCID mice).</p><p><b>RESULTS</b>We found that the 50% effective concentrations (EC(50)) of sIFNα against the replication of HIV-1 in MT4 cells was 0.06 ng/ml, representing stronger antiviral activity than interferon-α in vitro. In the hu-PBL-SCID mice, a dose-dependent protection pattern was observed: with 0.45 µg and 1.35 µg sIFNα daily treatments, parts of SCID mice were protected from HIV infection, whereas 2.25 µg sIFNα daily treatments resulted in a terminally complete protection.</p><p><b>CONCLUSIONS</b>sIFNα shows good anti-HIV activity both in vitro and in SCID mice, may be a promising anti-HIV agent deserving clinical investigation, especially considering the potential of IFN-α to inhibit HIV replication in patients infected with drug-resistant variants or co-infected with hepatitis C virus (HCV).</p>

Comparative proteome analysis of human papillomavirus-infected cervical specimens and the difference between the high- and low-risk genotypes of human papillomavirus / 中国医学科学院学报

<p><b>OBJECTIVE</b>To perform an comparative proteome analysis of human papillomavirus-infected cervical specimens and to investigate different expressions between high- and low-risk genotypes.</p><p><b>METHODS</b>The cervical specimens were divided into two groups (cervical intraepithelial neoplasia group and condyloma acuminatum group) according to their genotypes. Using comparative proteome technology, high-risk human papillomavirus-infected cervical intraepithelial neoplasia, low-risk human papillomavirus-infected condyloma acuminatum, and normal cervical intraepithelial tissue were compared. The differential expression protein spots were identified by mass spectrometry.</p><p><b>RESULTS</b>Totally 26 differential spots were selected and analyzed, and 22 peptide mass fingerprints (PMF) maps were obtained by MALDI-TOF-MS. Eighteen proteins were preliminarily identified after searching the NCBInr database. The function information of these 18 proteins mainly involved cell metabolism, signal transduction, cell secretion, cell cytoskeleton construction, cell proliferation, and apoptosis.</p><p><b>CONCLUSION</b>The proteomic expressions after the cervical infection of high- or low-risk genotype of human papillomavirus are obviously different.</p>

Study on genotypic resistance mutations to antiretroviral drugs on HIV strains of treated and treatment-naive HIV-1 infectious patients in Hubei province / 中华流行病学杂志

<p><b>OBJECTIVE</b>To study the drug resistance status on HIV-1 patients who had been treated with highly active antiretroviral therapy (HAART) and those treatment-naive ones in Hubei province.</p><p><b>METHODS</b>Nested polymerase chain reaction (PCR) was used to amplify 2 kb DNA fragment in HIV pol gene from peripheral blood of the HIV infected patients and the PCR products were sequenced. The sequences were compared to the Stanford HIV drug resistance database.</p><p><b>RESULTS</b>Nineteen patients were treated with regimens composed of two Nucleoside Reverse Transcriptase Inhibitors (NRTIs) and one Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI), with 25 patients as treatment-naive. Some protease (PR) drug-resistant mutations were found in these samples, such as D30N (2.27%), D30G (2.27%), M46I (4.55%), M46N (2.27%), I47V (4.55%), I84V (4.55%), I84L (2.27%), N88S (2.27%) and L90S (2.27%) that all belonged to major drug-resistant but A71T (29.55%) belonged to minor resistance mutations Five treated patients were detected having mutations associated RT drug resistance: M41L (5.26%), A62V (5.26%),D67N (5.26%), L210W (5.26%), T215Y (15.79%); K103E (5.26%), K103N (10.53%), Y181C (5.26%), G190A (5.26%), K238N (5.26%), while five treatment-naive patients were detected to have had mutations associated RT drug resistance M184V (4%), K65N (4%), Y115M (4%), F116L (4%), M184I (4%), V179D (4%), G190R (4%).Some additional mutations were detected in RT whose role involve in drug resistance still remained unknown. F214L was positively associated with HAART treatment (P = 0.03).</p><p><b>CONCLUSION</b>Significant differences were found between drug resistance mutations to RTIs in treated and treat-naive patients in Hubei province,indicating that drugs had affected the occurrence of drug resistance mutations. At the same time, novel RT mutations F214L might be associated with HAART or some other drugs.</p>