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.

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.

Interferons (IFNs) are natural proteins produced by wide variety of cells in response to viral infection or other biological inducers, and they execute diversified functions as antiviral defense, immune activation and cell growth regulation. Four genes encoding porcine interferons (PoIFN), PoIFN-alpha, PoIFN-gamma, PoIFN-alphagamma or PolFN-omega, were cloned and sequenced. The four types of porcine interferon genes were subcloned into the pET-His vector, and expressed in Escherichia coli Rosetta (DE3). The recombinant products were purified and renaturalized from inclusion bodies to obtain a native state of well biological activity. Antiviral activity assays for porcine interferons were performed and evaluated by standard procedures in following cell/virus test systems: Marc-145/PRRSV, Marc-145/VSV, PK-15/VSV, Vero/VSV or MDBK/VSV. The data showed that both PoIFN-alpha and PoIFN-alpagamma demonstrated significant antiviral activities, and the titer of them against PRRSV was up to 10(8) U/mg. PoIFN-gamma had approximately half or one-thirds antiviral activity of PoIFN-alpha. PoIFN-omega showed inconspicuous antiviral activity.
Amino Acid Sequence ; Animals ; Antiviral Agents ; pharmacology ; Cloning, Molecular ; Escherichia coli ; genetics ; metabolism ; Interferon Type I ; biosynthesis ; genetics ; pharmacology ; Interferon-gamma ; biosynthesis ; genetics ; pharmacology ; Molecular Sequence Data ; Porcine respiratory and reproductive syndrome virus ; drug effects ; Recombinant Proteins ; biosynthesis ; genetics ; pharmacology ; Swine