High risk populations and HIV-1 infection in China

China is currently experiencing one of the most rapidly expanding HIV epidemics in the world. Although the overall prevalence rate is still low, with a population of 1.3 billion, high-risk factors which have contributed to the HIV/AIDS epidemics worldwide continue to prevail in China, including a high rate of injecting drug use and needle sharing,commercial sex with low rates of condom use, and concurrent sex with both commercial sex workers and noncommercial casual or steady sex partners. In addition, there are increasing “double risk“ populations overlapping drug users and sex workers, as well as increasing rates of STDs and HIV among high-risk populations. Sexual transmission,therefore, may serve as a bridge connecting high-risk populations with general populations. There is an urgent need to prevent the spread of HIV from these high-risk populations into the general population of China.     

High risk populations and HIV-1 infection in China

INTRODUCTION HIV has spread to all of China’s 31 provinces, autono- mous regions and municipalities, creating one of the fast- est-growing HIV/AIDS epidemics in the world [1,2]. The HIV/AIDS epidemic in China has gone through three phases: the Entry Phase (1985 -1988), the Spreading Phase (1989-1994) and the Expansion Phase (1995- present). The striking increase of HIV-1 infections over the past few years may herald entry into a new fourth phase that will include much larger nu…     

High risk populations and HIV-1 infection in China

China is currently experiencing one of the most rapidly expanding HIV epidemics in the world. Although the overall prevalence rate is still low, with a population of 1.3 billion, high-risk factors which have contributed to the HIV/AIDS epidemics worldwide continue to prevail in China, including a high rate of injecting drug use and needle sharing, commercial sex with low rates of condom use, and concurrent sex with both commercial sex workers and non-commercial casual or steady sex partners. In addition, there are increasing "double risk" populations overlapping drug users and sex workers, as well as increasing rates of STDs and HIV among high-risk populations. Sexual transmission, therefore, may serve as a bridge connecting high-risk populations with general populations. There is an urgent need to prevent the spread of HIV from these high-risk populations into the general population of China.     

Global human genetics of HIV-1 infection and China

Genetic polymorphisms in human genes can influence the risk for HIV-1 infection and disease progression, although the reported effects of these alleles have been inconsistent. This review highlights the recent discoveries on global and Chinese genetic polymorphisms and their association with HIV-1 transmission and disease progression.     

Global human genetics of HIV-1 infection and China

Genetic polymorphisms in human genes can influence the risk for HIV-1 infection and disease progression, although the reported effects of these alleles have been inconsistent. This review highlights the recent discoveries on global and Chinese genetic polymorphisms and their association with HIV-1 transmission and disease progression.     

Global human genetics of HIV-1 infection and China

INTRODUCTION HIV-1 infection results in a variety of clinical outcomes. The majority of HIV-1 infected individuals progress to AIDS within 5 to 10 years, some progress rapidly to AIDS (termed rapid progressors) while others progress to AIDS slowly (slow p…     

Prevalence and risk factors for Helicobacter pylori infection in Chinese populations

Background:  The prevalence of Helicobacter pylori is higher in developing countries. The aim of this study was to investigate the prevalence and risk factors of H. pylori infection in areas with high prevalence of gastric cancer in Jiangsu Province, China.
Methods:  A prospective epidemiologic survey of H. pylori infection was accomplished in a natural population of 1457 individuals in Xiangshui and Gaoyou counties, Jiangsu Province, China. Questionnaires and laboratory tests for H. pylori infection (¹³C-urea breath test and serum IgG antibodies to H. pylori ) were used and performed, respectively.
Result:  Among 1371 subjects who completed questionnaires and H. pylori detection, 851 (62%) were H. pylori positive. The prevalence reached a peak at the age of 30–40 years (67%). There was no sex difference. The annual family income level was shown to be positively correlated with the risk of H. pylori infection. The prevalence of H. pylori infection was also associated with family size, education level, and several diet-related factors, such as the number of times cooked rice and potatoes eaten per week, and a family history of stomach diseases. Compared to nonsymptomatic individuals, people with dyspeptic symptoms (nausea, vomiting, and belching) presented a low prevalence of H. pylori infection. No association between H. pylori prevalence and smoking or drinking was found. Using multivariate logistic regression analysis, annual family income and education level were the independent predictors for H. pylori infection.
Conclusion:  High prevalence of H. pylori infection was found in areas with a high risk of gastric cancer and was related to several risk factors. The underlying mechanisms need to be further investigated.     

Genetic and neutralization sensitivity of diverse HIV-1 env clones from chronically infected patients in China

As HIV-1 continues to spread in China from traditional high risk populations to the general public, its genetic makeup has become increasingly complex. However, the impact of these genetic changes on the biological and neutralization sensitivity of the virus is unknown. The current study aims to characterize the genetic, biological, and neutralization sensitivity of HIV-1 identified in China between 2004 and 2007. Based on a total of 107 full-length envelope genes obtained directly from the infected patients, we found that those viruses fell into three major genetic groups: CRF01_AE, subtype B', and subtype C/CRF07_BC/CRF08_BC/B'C. Pseudotyped viruses built upon the viable env genes have demonstrated their substantial variability in mediating viral entry and in sensitivity to neutralization by subtype-specific plasma pools and broadly neutralizing monoclonal antibodies (bnmAb). Many viruses are resistant to one or more bnmAb, including those known to have high potency against diverse viruses from outside China. Sequence and structural analysis has revealed several mechanisms by which these resistant viruses escape recognition from bnmAb. We believe that these results will help us to better understand the impact of genetic diversity on the neutralizing sensitivity of the viruses and to facilitate the design of immunogens capable of eliciting antibodies with potency and breadth similar to those of bnmAb.     

我国首次发现的HIV-1和HIV-2双重感染样品中病毒部分基因的序列特征分析

上海市卫生检疫局送检了一例HIV - 1和HIV - 2抗体检测均呈阳性的双重感染样品 ,对其感染的HIV前病毒的 gag和env基因区进行了序列分析 ,首次阐明我国发现的HIV双重感染样品的HIV部分基因特征。从HIV感染者淋巴细胞 (peripheralbloodmononuclearcells,PBMC)中提取前病毒DNA ,分别使用HIV 1和HIV 2特异性引物用套式PCR扩增HIV 1和HIV 2的部分基因区。PCR产物不经克隆直接测序 ,经GenBank检索并使用GCG软件包进行序列分析。结果表明 ,其中感染的HIV 2毒株中gag基因区与德国株HI2PEI2KR相似 ,基因离散率仅为8 1% ,env基因C2 -V3区与来自几内亚比绍的HIV 2U0 5 35 8株最近 ,离散率为 13 0 4% ,在其 gp36区发现与HIV 2U0 5 35 8基因离散率为 10 6 3% ,两个毒株均属HIV 2中的A亚型。而其HIV 1型毒株在 gag和env区都与从尼日利亚分离的H92NG0 83株相似 ,属HIV 1的G亚型。本文首次对我国发现的HIV 2型毒株进行了主要基因区的序列分析 ,表明在非洲较常见的HIV 2A亚型和HIV 1G亚型毒株 ,已随援外劳工传入我国。     

Plectin regulates the signaling and trafficking of the HIV-1 co-receptor CXCR4 and plays a role in HIV-1 infection

The CXC chemokine CXCL12 and its cognate receptor CXCR4 play an important role in inflammation, human immunodeficiency virus (HIV) infection and cancer metastasis. The signal transduction and intracellular trafficking of CXCR4 are involved in these functions, but the underlying mechanisms remain incompletely understood. In the present study, we demonstrated that the CXCR4 formed a complex with the cytolinker protein plectin in a ligand-dependent manner in HEK293 cells stably expressing CXCR4. The glutathione-S-transferase (GST)-CXCR4 C-terminal fusion proteins co-precipitated with the full-length and the N-terminal fragments of plectin isoform 1 but not with the N-terminal deletion mutants of plectin isoform 1, thereby suggesting an interaction between the N-terminus of plectin and the C-terminus of CXCR4. This interaction was confirmed by confocal microscopic reconstructions showing co-distribution of these two proteins in the internal vesicles after ligand-induced internalization of CXCR4 in HEK293 cells stably expressing CXCR4. Knockdown of plectin with RNA interference (RNAi) significantly inhibited ligand-dependent CXCR4 internalization and attenuated CXCR4-mediated intracellular calcium mobilization and activation of extracellular signal regulated kinase 1/2 (ERK1/2). CXCL12-induced chemotaxis of HEK293 cells stably expressing CXCR4 and of Jurkat T cells was inhibited by the plectin RNAi. Moreover, CXCR4 tropic HIV-1 infection in MAGI (HeLa-CD4-LTR-Gal) cells was inhibited by the RNAi of plectin. Thus, plectin appears to interact with CXCR4 and plays an important role in CXCR4 signaling and trafficking and HIV-1 infection.     

Guatemalan plants extracts as virucides against HIV-1 infection

Prevention methods to avoid transmission of pathogens, including HIV, are crucial in the control of infectious diseases, not only to block epidemic spread but to avoid long-term treatments leading to emergence of resistances and drug associated side effects. Together with vaccine development, the discovery of new virucidal agents represents a research priority in this setting. In the screening of new compounds with antiviral activity, three Guatemalan plant extracts from Justicia reptans, Neurolaena lobata and Pouteria viridis were evaluated with a classic antiviral assay and were found to inhibit HIV replication. This activity was corroborated by an original recombinant virus assay, leading us to perform a deeper study of the virucidal activity. Active fractions were non-toxic in vitro and also inhibited other enveloped viruses. Moreover, these fractions were able to inhibit the transfer of HIV from dendritic cells (DCs) to lymphocytes, that represents the main way of HIV spread in vivo.     

High level serum neutralizing antibody against HIV-1 in Chinese long-term non-progressors

NAb have been considered to be an important component of a protective immune response to HIV-1, yet the relationship between the capacity of HIV-1 NAb, the conserved neutralization epitopes and disease progression has been unclear. To gain a better understanding of the protective roles that NAb and conserved neutralization epitopes could play in LTNP, twenty-eight HIV-1-infected subjects were investigated by evaluation of the concentrations of HIV-1 NAb and conserved neutralization epitopes, using single-round PBMC neutralization assay and sequencing. Our study revealed that the concentration of NAb in LTNP was significantly higher than that in subjects with asymptomatic HIV (P < 0.05) and AIDS (P < 0.01). No amino acids substitutions were found in the conserved epitopes of the HIV-1 gp120 region in LTNP, whereas the viruses circulating both in persons with asymptomatic HIV and those with AIDS had amino acid substitutions in their conserved neutralization epitopes. This study suggests that high levels of NAb and stable epitopes in gp120 could play a crucial role in protection against disease progression.     

Drug-induced lipotoxicity: Lipodystrophy associated with HIV-1 infection and antiretroviral treatment

A subset of HIV-1-infected patients undergoing antiretroviral treatment develops a lipodystrophy syndrome. It is characterized by loss of peripheral subcutaneous adipose tissue (face, limbs, buttocks), visceral fat accumulation, and, in some cases, lipomatosis, especially in the dorsocervical area. In addition, these patients show metabolic alterations reminiscent of the metabolic syndrome, particularly dyslipidemia and insulin resistance. These alterations lead to enhanced cardiovascular risk in patients and favor the development of diabetes. Although a complex combination of HIV-1 infection and drug treatment-related events triggers the syndrome, lipotoxicity appears to contribute to the development of the syndrome. Active lipolysis in subcutaneous fat, combined with impaired fat storage capacity in the subcutaneous depot, drive ectopic deposition of lipids, either in the visceral depot or in nonadipose sites. Both hepatic steatosis and increased lipid content in skeletal muscle take place and surely contribute to systemic metabolic alterations, especially insulin resistance. Pancreatic function may also be affected by the exposure to high levels of fatty acids; together with direct effects of antiretroviral drugs, this may contribute to impaired insulin release and a prodiabetic state in the patients. Addressing lipotoxicity as a pathogenic actor in the lipodystrophy syndrome should be considered in strategies for treating and/or preventing the morphological alterations and systemic metabolic disturbances associated with lipodystrophy.     

Global human genetics of HIV-1 infection and China

Genetic polymorphisms in human genes can influence the risk for HIV-1 infection and disease progression, although the reported effects of these alleles have been inconsistent. This review highlights the recent discoveries on global and Chinese genetic polymorphisms and their association with HIV-1 transmission and disease progression.     

Advance in treatment strategy and immune reconstruction against HIV-1 infection

HIV-1 can be considered an infection of the immune system, resulting in progressive and ultimately profound immune suppression. The availability of highly active antiretroviral therapy (HAART) has resulted in dramatic changes in the disease course in persons fortunate enough to have access to these medications, but long-term therapy is limited by the development of resistance as well as toxicities of the potent medication regimens. Emerging data indicate that individuals who have non-progressive clinical course control HIV-1 immunologically. This has bolstered hope that the immune response might be effectively augmented in persons with HIV infection. Recent data indicating that immediate treatment of acute infection leads to augmentation of antiviral immune responses have provided evidence that the immune system might be enhanced in certain situations. Therefore, investigation in the reconstitution of anti-HIV immune response in patients under HAART should provide encouragement for continuing to explore methods to obtain meaningful and durable immune enhancement as an adjunct to HAART in HIV-1 infection.     

Evaluating the potential of IL-27 as a novel therapeutic agent in HIV-1 infection

Interleukin 27 (IL-27) is an immunomodulatory cytokine with important roles in both the innate and adaptive immune systems. In the last five years, the addition of exogenous IL-27 to primary cell cultures has been demonstrated to decrease HIV-1 replication in a number of cell types including peripheral blood mononuclear cells (PBMCs), CD4+ T cells, macrophages and dendritic cells. These in vitro findings suggest that IL-27 may have therapeutic value in the setting of HIV-1 infection. In this review, we describe the current knowledge of the biology of IL-27, its effects primarily on HIV-1 replication but also in other viral infections and explore its potential role as a therapeutic cytokine for the treatment of patients with HIV-1 infection.     

Pollution and health risk assessment of heavy metals in urban soil in China

The pollution and potential health risk due to lifetime exposure to heavy metals in urban soil of China were evaluated, based on the urban soil samples collected from published papers from 2005 to 2014. The contamination levels were in the order of Cd > Hg > Cu > Zn > Pb >As > Ni > Cr, and Hg and Cd fell into the category of “moderately contaminated” to “heavily contaminated.” The non-carcinogenic risk for different populations varied greatly, among which children faced high risk, and then the adult female and adult male followed. The hazard index (non-carcinogenic risk) higher than 1.00 occurred in Shanghai, Gansu, Qinghai, Hunan, and Anhui, whereas most of those in northern and western China had low risks. For the carcinogenic risk, Anhui and Ningxia provinces had urban soils exceeding the safe reference (1 × 10^?6–1 × 10^?4). Qinghai and Gansu had high carcinogenic risks since their risk indexes were much closer to the reference, and the others were in low risk.