Epidemiology of sexually transmitted infections, HIV, and related high-risk behaviors among female sex workers in Guangxi Autonomous Region, China.

This study assessed the epidemiology of sexually transmitted infections (STIs), HIV, and associated risk factors among female sex workers (FSWs) in Guangxi autonomous region, China. A cross-sectional study of 488 FSWs was conducted using a structured questionnaire to collect sociodemographic and behavioral information. Biological specimens from subjects were sampled to detect various STIs and HIV infection. Among FSWs, the prevalence rates of syphilis, Neisseria gonorrhoeae, Chlamydia trachomatis, genital herpes, condyloma acuminate, and HIV were 7.2%, 1.8%, 18.2%, 0.4%, 2.3%, and 0.8%, respectively. The prevalence rates of single, double, and triple infections were 22.3%, 3.9%, and 0.20%, respectively. Multivariate analysis indicated that STIs and HIV infection was independently related to low education level (OR = 7.244; 95% CI = 3.031-17.213; P < 0.001), low knowledge of STIs/HIV (OR = 0.191; 95% CI = 0.108-0.337; P < 0.001), low-grade working place (OR = 1.64; 95%CI = 1.016-2.648; P = 0.046), and no condom use during the last sexual intercourse (OR = 0.199; 95% CI = 0.113-0.350; P < 0.001). The prevalence of STIs is high among FSWs in Guangxi, is accompanied by a 0.8% HIV-positive rate, and may be largely related to high-risk sexual behaviors. Future interventions should be focused on the reduction of risk factors, including promotion of condom use and improvement of knowledge of STIs and HIV among FSWs.

Discovery and characterization of substituted diphenyl heterocyclic compounds as potent and selective inhibitors of hepatitis C virus replication.

A novel small-molecule inhibitor, referred to here as R706, was discovered in a high-throughput screen of chemical libraries against Huh-7-derived replicon cells carrying autonomously replicating subgenomic RNA of hepatitis C virus (HCV). R706 was highly potent in blocking HCV RNA replication as measured by real-time reverse transcription-PCR and Western blotting of R706-treated replicon cells. Structure-activity iterations of the R706 series yielded a lead compound, R803, that was more potent and highly specific for HCV replication, with no significant inhibitory activity against a panel of HCV-related positive-stranded RNA viruses. Furthermore, HCV genotype 1 replicons displayed markedly higher sensitivity to R803 treatment than a genotype 2a-derived replicon. In addition, R803 was tested by a panel of biochemical and cell-based assays for on-target and off-target activities, and the data suggested that the compound had a therapeutic window close to 100-fold, while its exact mechanism of action remained elusive. We found that R803 was more effective than alpha interferon (IFN-alpha) at blocking HCV RNA replication in the replicon model. In combination studies, R803 showed a weak synergistic effect with IFN-alpha/ribavirin but only additive effects with a protease inhibitor and an allosteric inhibitor of RNA-dependent RNA polymerase (20). We conclude that R803 and related heterocyclic compounds constitute a new class of HCV-specific inhibitors that could potentially be developed as a treatment for HCV infection.

Detection of Acute and Established HIV Infections in Sexually Transmitted Disease Clinics in Guangxi, China: Implications for Screening and Prevention of HIV Infection.

BACKGROUND: Human immunodeficiency virus (HIV) has spread throughout China and to some degree has penetrated the general heterosexual population in some regions. METHODS: A cross-sectional survey of 11,461 sexually transmitted disease (STD) clinic attendees in 8 cities in Guangxi, China, was conducted for syphilis and for acute and established HIV infections. RESULTS: The prevalence of acute and established HIV infections was 1.2% among the participants. Five acute (preseroconversion) HIV infections were detected. Multivariate analysis showed that HIV infection was independently related to unmarried status (odds ratio [OR], 1.73 [95% confidence interval {CI}, 1.00-2.99), less education (OR for less than primary school, 4.21 [90% CI, 1.21-14.58]), residence in city A (OR, 11.48 [95% CI, 2.05-64.31]) or city B (OR, 7.93 [95% CI, 1.75-35.91]), working in the entertainment industry (OR, 3.98 [95% CI, 1.14-13.88]), injection drug use (OR, 25.09 [95% CI, 10.43-60.39]), no condom use during most recent sexual intercourse (OR, 4.97 [95% CI, 1.38-17.88]), and syphilitic infection (OR, 1.91 [95% CI, 1.03-3.56]). CONCLUSIONS: HIV prevalence in STD clinics is significantly greater than that in the general population, and subjects were identified who would be missed by conventional surveillance. China's nationwide system of public STD clinics, which reach down to the township level, should be used for HIV control programs.

Risk of syphilis in STI clinic patients: a cross-sectional study of 11,500 cases in Guangxi, China.

OBJECTIVE: To measure prevalence of syphilis among the STI clinic population in Guangxi, China, and to assess the socioeconomic and behavioural characteristics associated with the infection. METHODS: We undertook a cross-sectional survey and syphilis and HIV serologic testing among 11 473 patients attending 14 community and hospital-based dermatovenereal clinics across eight cities in Guangxi between December 2004 and February 2006. RESULTS: 1297 (11.9%) patients demonstrated positive toludine red unheated serum test and Treponema pallidum particle agglutination results with serologic testing. A total of 58% (752) of seropositive subjects presented with a genital ulcer, palmar/plantar rash or inguinal lymphadenopathy. Female sex (OR = 2.23, 95% confidence intervals (CI) = 1.69 to 3.00, p<0.001), less education (middle school, OR = 1.70, 95% CI = 1.11 to 2.62, p = 0.023; primary school or less, OR = 1.98, 95% CI = 1.13 to 3.46, p = 0.017) and high annual income (OR = 1.91, 95% CI = 1.18 to 3.10, p = 0.009 for >30 000 RMB yuan) were associated with serologically positive status. Syphilis infection was significantly more prevalent in city 2 (19.5%, OR = 3.07, 95% CI = 1.83 to 5.16, p<0.001), city 4 (16.6%, OR = 1.90, 95% CI = 1.10 to 3.28, p = 0.011) and city 8 (13.8%, OR = 1.83, 95% CI = 1.13 to 2.97, p = 0.006). A total of 40.1% (532) of infected subjects engaged in commercial sex and increased rates of the infection was associated with multiple sexual partners (OR = 1.54, 95% CI = 1.16 to 2.06, p = 0.003). A total of 1.2% (133) of participants carried laboratory markers for HIV and 1.8% (23) of patients with syphilis were positive for HIV. CONCLUSIONS: Syphilis infection has reached alarming rates in China's STI clinic population, suggesting a generalised spread of the disease through commercial sex and bridging populations. Syphilis control is deserving of China's highest priority. Universal screening for syphilis and HIV testing in STI clinics should be considered as measures for control.

The poxvirus p28 virulence factor is an E3 ubiquitin ligase.

A majority of the orthopoxviruses, including the variola virus that causes the dreaded smallpox disease, encode a highly conserved 28-kDa protein with a classic RING finger sequence motif (C(3)HC(4)) at their carboxyl-terminal domains. The RING domain of p28 has been shown to be a critical determinant of viral virulence for the ectromelia virus (mousepox virus) in a murine infection model (Senkevich, T. G., Koonin, E. V., and Buller, R. M. (1994) Virology 198, 118-128). Here, we demonstrate that the p28 proteins encoded by the ectromelia virus and the variola virus possess E3 ubiquitin ligase activity in biochemical assays as well as in cultured mammalian cells. Point mutations disrupting the RING finger domain of p28 completely abolish its E3 ligase activity. In addition, p28 functions cooperatively with Ubc4 and UbcH5c, the E2 conjugating enzymes involved in 26 S proteasome degradation of protein targets. Moreover, p28 catalyzes the formation of Lys-63-linked polyubiquitin chains in the presence of Ubc13/Uev1A, a heterodimeric E2 conjugating enzyme, indicating that p28 may regulate the biological activity of its cognate viral and/or host cell target(s) by Lys-63-linked ubiquitin multimers. We thus conclude that the poxvirus p28 virulence factor is a new member of the RING finger E3 ubiquitin ligase family and has a unique polyubiquitylation activity. We propose that the E3 ligase activity of the p28 virulence factor may be targeted for therapeutic intervention against infections by the variola virus and other poxviruses.

Functional Difference between N Domain and C Domain of hEGF and hTGF-alpha.

By exchanging the N domain and C domain of hEGF and hTGF-alpha genes by PCR, two chimeras E-TGF(EGF(1-32)-TGF-alpha(34-50))and T-EGF(TGF-alpha(1-33)-EGF(33-53))were constructed. The wild and chimeric molecules were expressed in E.coli under phoA system. The expressed hEGF, hTGF-alpha and two chimeras were purified. The EGF receptor competitive binding affinity of the four molecules was hEGF > hTGF-alpha and E-TGF > T-EGF and the cell proliferation stimulating activity of them was hTGF-alpha and E-TGF > T-EGF > hEGF. The result suggests that the N domain of hEGF and hTGF-alpha may play a major role in receptor binding activity and C domain of them may be responsible for stimulating cell proliferation.