Down-regulation of HIV-1 Infection by Inhibition of the MAPK Signaling Pathway / 中国病毒学·英文版

The human immunodeficiency virus type 1(HIV-1)can interact with and exploit the host cellular machinery to replicate and propagate itself.Numerous studies have shown that the Mitogen-activated protein kinase(MAPK)signal pathway can positively regulate the replication of HIV-1,but exactly how each MAPK pathway affects HIV-1 infection and replication is not understood.In this study,we used the Extracellular signal-regulated kinase(ERK)pathway inhibitor,PD98059,the Jun N-terminal kinase(JNK)pathway inhibitor,SP600125,and the p38 pathway inhibitor,SB203580,to investigate the roles of these pathways in HIV-1replication.We found that application of PD98059 results in a strong VSV-G pseudotyped HIV-1NL4-3 luciferase reporter virus and HIV-1NL4-3 virus inhibition activity.In addition,SB203580 and SP600125 also elicited marked VSV-G pseudotyped HIV-1NL4-3 luciferase reporter virus inhibition activity but no HIV-1NL4-3 virus inhibition activity.We also found that SB203580 and SP600125 can enhance the HIV-1 inhibition activity of PD98059when cells were treated with all three MAPK pathway inhibitors in combination.Finally,we show that HIV-1virus inhibition activity of the MAPK pathway inhibitors was the result of the negative regulation of HIV-1 LTR promoter activity.

Emerging Trends of Drug-Resistant HIV-1 among Drug-Treated Patients in Former Blood Donors in Hubei, China: a Three-Year Surveillance from 2004 to 2006 / 中国病毒学·英文版

This study aimed to evaluate emerging trends of drug resistance to nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) among 290 former blood donor HIV-1 infected patients in Hubei,China,from 2004 to 2006,all of whom had received anti-HIV-1 therapy.The presence of NRTI- and NNRTI-associated mutations were established by sequencing; genotypic and predicted phenotypic drug resistance were evaluated using HIVdb Program version 5.0.1 (http://hivdb.stanford.edu/pages/algs/HIVdb.html).Genotypic drug resistance analysis showed significant increases in percentages of patients carrying HIV-1 strains with M41L,T215Y/F,D67N,K103N,G190A/S,Y181C/F or L210W mutations.Of the variants' predicted phenotypic drug resistance,highly significant increases were detected in percentages of patients carrying HIV-1 with high resistance to zidovudine (AZT) or stavudine (D4T) in NRTIs,and to delavirdine (DLV),efavirenz (EFV) or nevirapine (NVP) in NNRTIs; intermediate resistance to abacavir (ABC),AZT,D4/T,didanosine (DDI) or tenofovir disoproxil fumarate (TDF) in NRTIs,and to etravirine (ETR) in NNRTIs; and low and potential low resistance to lamivudine (3TC),ABC,emtricitabine (FTC) or TDF in NRTIs,and to ETR in NNRTIs.