Evolutionary selection associated with the multi-function of overlapping genes in the hepatitis B virus

It is a challenge to understand the discrete roles of each point mutation in viral evolution, but overlapping genes provide an excellent entrance for the investigation of this complicated process. We obtained 132 sequences from the largest overlapping region in the HBV genome. Based on the genetic divergence between genotypes B and C, we distinguished a set of related footprint mutations that are believed to be responsible for historical selection events. Examining the mutations in the functional domains, we found that the virus has adopted a coherent strategy in its evolutionary process that can be summarized as follows: (1) the distribution of mutations was non-random throughout the overlapping region, and more mutations were preserved in the sequence when one of the genes was under relaxed selection; (2) the viral domains were subject to different selective pressures; for instance, the PreS1 domain underwent a strict selection, whereas the overlapped Spacer domain was relatively relaxed with obvious tolerance of non-synonymous mutations with a high dN/dS ratio; (3) different selective pressures on two codon sites ultimately determined that every mutation persevered at a proper position. Taken together, the functional constraints of protein domains are believed to be primarily responsible for the different selection patterns exhibited by the distribution of mutations and amino acid changes in the region where overlapping genes reside.     

Epidemiological investigations of human rabies in China

Background  

The epidemic of rabies showed a rising trend in China in recent years. To identify the potential factors involved in the emergence, we investigated and analyzed the status and characteristics of human rabies between 1996 and 2008. Moreover, the status of rabies infection and vaccination in dogs, and prophylaxis of humans after rabies exposure were analyzed.     

Hantavirus Infections in Humans and Animals, China

Hemorrhagic fever with renal syndrome (HFRS) is a serious public health problem in the People’s Republic of China. Although 7 sero/genotypes of hantaviruses have been found in rodents, only Hantaan virus (carried by Apodemus agrarius mice) and Seoul virus (carried by Rattus norvegicus rats) reportedly cause disease in humans. During 1950–2007, a total of 1,557,622 cases of HFRS in humans and 46,427 deaths (3%) were reported in China. HFRS has been reported in 29 of 31 provinces in China. After implementation of comprehensive preventive measures, including vaccination, in the past decade in China, incidence of HFRS has dramatically decreased; only 11,248 HFRS cases were reported in 2007. Mortality rates also declined from the highest level of 14.2% in 1969 to ≈1% during 1995–2007. However, the numbers of HFRS cases and deaths in China remain the highest in the world.     

Rapid identification of Streptococcus pneumoniae serotypes by cpsB gene-based sequetyping combined with multiplex PCR

Background/purposeStreptococcus pneumoniae is an important human pathogen that causes invasive infections in adults and children. Accurate serotyping is important to study its epidemiological distribution and to assess vaccine efficacy.MethodsInvasive S. pneumoniae isolates (n = 300) from 27 teaching hospitals in China were studied. The Quellung reaction was used as the gold standard to identify the S. pneumoniae serotypes. Subsequently, multiplex PCR and cpsB gene-based sequetyping methods were used to identify the serotypes.ResultsBased on the Quellung reaction, 299 S. pneumoniae isolates were accurately identified to the serotype level and 40 different serotypes were detected. Only one strain was non-typeable, and five most common serotypes were identified: 23F (43, 14.3%), 19A (41, 13.7%), 19F (41, 13.7%), 3 (31, 10.3%), and 14 (27, 9.0%). Overall, the multiplex PCR method identified 73.3 and 20.7% of the isolates to the serotype and cluster levels, respectively, with 1.7% of the isolates misidentified. In contrast, the cpsB sequetyping method identified 59.0 and 30.3% of the isolates to the serotype and cluster levels, respectively, and 7% were misidentified.ConclusionsThe cpsB gene sequetyping method combined with multiplex PCR, can greatly improve the accuracy and efficiency of serotyping, besides reducing the associated costs.     

凉山彝族自治州HIV/AIDS抗病毒治疗前HIV-1耐药情况及其影响因素分析

目的 了解凉山彝族自治州（凉山州）HIV/AIDS抗病毒治疗前HIV-1耐药情况及其影响因素,为预防HIV-1耐药毒株的传播提供参考依据。方法 分别于2017年1月1日至6月30日、2018年1月1日至6月30日在凉山州开展HIV/AIDS抗病毒治疗前HIV-1耐药的横断面调查。提取获得HIV-1 pol基因区序列,根据2014年WHO耐药监测指南的推荐标准,应用HyPhy 2.2.4和Cytoscape 3.6.1软件进行HIV-1耐药毒株传播网络分析。结果 研究对象464例HIV/AIDS,HIV-1毒株为CRF07_BC亚型的占88.6%（411/464）,总的HIV-1耐药率为9.9%（46/464）,非核苷类反转录酶抑制剂（NNRTI）、核苷类反转录酶抑制剂（NRTI）和蛋白酶抑制剂（PI）耐药率分别为6.7%（31/464）、1.9%（9/464）和0.4%（2/464）;有1组HIV-1新型重组毒株URF_01BC亚型独立成簇并携带相关耐药突变位点;多因素logistic回归分析结果显示,与异性性传播人群相比,注射吸毒人群的HIV-1耐药风险较高（aOR=3.03,95% CI：1.40～6.54）。结论 凉山州HIV/AIDS抗病毒治疗前的HIV-1耐药率较高,且有新型重组毒株URF_01BC亚型携带相关耐药突变位点的成簇传播,建议加强HIV-1耐药毒株传播的预防工作。     

Nucleic acid vaccines for hepatitis B and C virus

Hepatitis B virus (HBV) and Hepatitis C virus (HCV) infections accounts for an important global health problem affecting over 250 million people all around the world. They can cause acute, transient and chronic infections in the human liver. Chronic infection of liver can lead to its failure or cancer. To deal with this problem, alternative approaches or strategies to inhibit these infections have already been started. DNA and mRNA-based vaccination will increase the efficacy and reduce toxicity in patients with Hepatitis B virus (HBV) and Hepatitis C virus (HCV) infections. Gene vaccines represent a promising alternative to conventional vaccine approaches because of their high potency, capacity for rapid development, low-cost manufacture and safe administration. MRNA-based vaccination is a method to elicit potent antigen-specific humoral and cell-mediated immune responses with a superior safety profile compared with DNA vaccines. Exploring the intricacies of these pathways can potentially help the researchers to explore newer vaccines. In this study, DNA and mRNA-based vaccination are introduced as an approach to treat Hepatitis B virus (HBV) and Hepatitis C virus (HCV) infections. DNA and mRNA-based vaccines as one of the most successful therapeutics are introduced and the clinical outcomes of their exploitation are explained.