Hepatitis C virus (HCV) is a model for the study of virus–host interaction and host cell responses to infection. Virus entry into hepatocytes is the first step in the HCV life cycle, and this process requires multiple receptors working together. The scavenger receptor class B type I (SR-BI) and claudin-1 (CLDN1), together with human cluster of differentiation (CD) 81 and occludin (OCLN), constitute the minimal set of HCV entry receptors. Nevertheless, HCV entry is a complex process involving multiple host signaling pathways that form a systematic regulatory network; this network is centrally controlled by upstream regulators epidermal growth factor receptor (EGFR) and transforming growth factor β receptor (TGFβ-R). Further feedback regulation and cell-to-cell spread of the virus contribute to the chronic maintenance of HCV infection. A comprehensive and accurate disclosure of this critical process should provide insights into the viral entry mechanism, and offer new strategies for treatment regimens and targets for HCV therapeutics.
1 January 2016 in Infection, Genetics and Evolution
An outbreak of dengue virus (DENV) occurred in Yunnan province. More than 2,000 individuals were infected from August to November 2013. In this study, we aimed to characterize the origin and prevalence of DENV in Dehong prefecture of Yunnan province using phylogenetic and evolutionary analyses of DENV strains collected from local patients and foreign travelers. A total of 41 DENV-positive serum samples were randomly collected from travelers who entered China at Ruili port or local patients with dengue fever in Dehong prefecture of Yunnan province, China. The envelope (E) gene of DENV was amplified and sequenced. The distributions and evolutionary characteristics of different genotypes were elucidated by phylogenetic and Bayesian analyses. Phylogenetically, all of the 41 DENV-positive samples could be classified into genotype I (43.9%) of serotype DENV-1 and the Asian I genotype (56.1%) of serotype DENV-2. DENV strains derived from local patients and foreign travelers were scattered equally within these two clusters. Furthermore, the DENV strains from the two populations exhibited high relatedness based on evolutionary characteristics. These results suggested that imported and local DENV strains occurring during the dengue outbreak in 2013 were highly related. Additionally, these data may suggest that this dengue outbreak was caused by a newly imported infection from the neighboring country of Myanmar.
Human Pegivirus-1 (HPgV-1) may have a beneficial impact on disease progression in human immunodeficiency virus-1 (HIV-1) infection. However, analysis of the genotypic diversity of HPgV-1 and its relevance to the progression of HIV-1 disease remains limited. A total of 1062 HIV-1-infected individuals were recruited in all sixteen prefectures of Yunnan province, China. The reverse transcription nested polymerase chain reaction (RT-nPCR), phylogenetic analyses, and clinical data analyses were used to detect HPgV-1 infection, determine genotype, and analyze HPgV-1 genotype impact on HIV-1 disease progression. The overall positive rate of HPgV-1 RNA was 23.4% (248/1062), and the frequency of HPgV-1 infection in injecting drug users (IDUs) (28.5%, 131/460) was significantly higher than in heterosexuals (19.4%, 117/602). Multiple genotypes were identified in 212 subjects with successful sequencing for the E2 gene, including genotype 7 (55.7%), genotype 3 (34.9%), genotype 4 (4.7%), genotype 2 (3.3%), and an unclassified group (1.4%). Moreover, genotype 7 predominated in IDUs, whereas genotype 3 was the most common in heterosexuals. Our results revealed that HPgV-1 genotype 7 groups exhibited significantly lower HIV-1 viral load and higher CD4+ cell counts. This finding suggests that HPgV-1 genotype 7 may be associated with a better progression of HIV-1 disease.
Yunnan is not only considered the region with the most concerning human immunodeficiency virus (HIV)-1 prevalence, but is also the central hub for the spread of HIV-1 from Southeast Asia to the other provinces of China. Yunnan has the highest proportion of entry travelers who have transmitted HIV from neighbored Southeast Asian countries to mainland of China. Between 2003 and 2012, we recruited 280,961 entry travelers at land ports located in 7 bordering prefectures respectively in the Yunnan Province for HIV-1 screening. Based on the detection of HIV-1 antibody, the HIV-1 infection rate was determined. Among the recruited entry travelers, 2380 were determined HIV-1 positive with infection rate of 0.85%. Travelers entering the Dehong port had the highest HIV-1 infection rate (5.12%), followed by those entering Baoshan (0.88%), Lincang (0.83%), and Honghe (0.71%). For all HIV-1 positive cases, travelers aged 21–30 and 31–40 were the most commonly infected individuals, accounting for 38.45% and 37.77% of all cases, respectively. The most common occupation of the infected population was driver (42.38%), and the proportion of industrials had increased yearly. Based on the reported risk factors, sexual transmission was the main HIV-1 infection route (77.11%) of this population. We have clarified the rate of HIV-1 infection among this bridge population. The characteristics of HIV-1 positive population and high geographical heterogeneity have provided the necessary epidemiological data for monitoring the HIV-1 epidemic among cross-border travelers in Yunnan and to further understand the cross-border spreading of the HIV-1 infection.