亚洲艾滋病疫情呈上升趋势

大规模的艾滋病疫情正在亚洲迅速蔓延．但却没有引起当地政府的警觉．专家警告说。

Sequence Variation in the Gp120 region of SHIV-CN97001 during in vivo Passage

SHIV-CN97001 played an important role in assessing the immune effect and strategy of the AIDS vaccine which included genes of the predominant prevalent HIV-1 strain in China. In this study, SHIV-CN97001 was in vivo passaged serially to construct pathogenic SHIV-CN97001/rhesus macaques model. To identify variation in the gp120 region of SHIV-CN97001 during passage, the fragments of gp120 gene were amplified by RT-PCR from the plasma of SHIV-CN97001 infected animals at the peak viral load time point and the gene distances (divergence, diversity) were calculated using DISTANCE. The analysis revealed that the genetic distances of SHIV-CN97001 in the third passage animals were the highest during in vivo passage. It had a relationship between viral divergence from the founder strain and viral replication ability. The nucleic acid sequence of the V3 region was highly conservative. All of the SHIV-CN97001 strains had V3 loop central motif (GPGQ) and were predicted to be using CCR5 co-receptor on the basis of the critical amino acids within V3 loop. These results show that there was no significant increase in the genetic distance during serial passage, and SHIV-CN97001 gp120 gene evolved toward ancestral states upon transmission to a new host. This could partly explain why there was no pathogenic viral strain obtained during in vivo passage.

Immunogenicity of DNA and Recombinant Sendai Virus Vaccines Expressing the HIV-1 gag Gene

Combinations of DNA and recombinant-viral-vector based vaccines are promising AIDS vaccine methods because of their potential for inducing cellular immune responses. It was found that Gag-specific cytotoxic lymphocyte (CTL) responses were associated with lowering viremia in an untreated HIV-1 infected cohort. The main objectives of our studies were the construction of DNA and recombinant Sendai virus vector (rSeV) vaccines containing a gag gene from the prevalent Thailand subtype B strain in China and trying to use these vaccines for therapeutic and prophylactic vaccines. The candidate plasmid DNA vaccine pcDNA3.1(+)-gag and recombinant Sendai virus vaccine (rSeV-gag) were constructed separately. It was verified by Western blotting analysis that both DNA and rSeV-gag vaccines expressed the HIV-1 Gag protein correctly and efficiently. Balb/c mice were immunized with these two vaccines in different administration schemes. HIV-1 Gag-specific CTL responses and antibody levels were detected by intracellular cytokine staining assay and enzyme-linked immunosorbant assay (ELISA) respectively. Combined vaccines in a DNA prime/rSeV-gag boost vaccination regimen induced the strongest and most long-lasting Gag-specific CTL and antibody responses. It maintained relatively high levels even 9 weeks post immunization. This data indicated that the prime-boost regimen with DNA and rSeV-gag vaccines may offer promising HIV vaccine regimens.

An Experimental Model for Screening Anti-AIDS Drugs with Bovine Immunodeficiency Virus

The assays for bovine immunodeficiency virus (BIV) induced syncytium formation and BIV long terminal repeat (LTR) directed luciferase (Luc) gene expression were applied to screen and evaluate anti AIDS drugs. Frequency of the syncytium formation and BIV LTR directed Luc activity were in proportion to the number of input BIV infected cells. AZT inhibited the syncytium formation and the BIV LTR directed Luc gene expression level. Its inhibitory effects were dosedependent with the IC 50 being 0.24 and 0.052 mmol / L, respectively.

The Comparison of Genetic Variation in the Envelope Protein Between Various Immunodeficiency Viruses and Equine Infectious Anemia Virus

The envelope protein （Env） of lentiviruses such as HIV, SIV, FIV and EIAV is larger than that of other retroviruses. The Chinese EIAV attenuated vaccine is based on Env and has helped to successfully control this virus, demonstrating that envelope is crucial for vaccine. We compared Env variation of the four kinds of lentiviruses. Phylogenetic analysis showed that the evolutionary relationship of Env between HIV and SIV was the closest and they appeared to descend from a common ancestor, and the relationship of HIV and EIAV was the furthest. EIAV had the shortest Env length and the least number of potential N-linked glyeosylation sites （PNGS） as well as glyeosylation density compared to various immunodefieiency viruses. However, HIV had the longest Env length and the most PNGS. Moreover, the alignment of HIV and SIV showed that PNGS were primarily distributed within extraeellular membrane protein gp120 rather than transmembrane gp41. It implies that the size difference among these viruses is associated with a lentivirus specific function and also the diversity of env. There arc low levels of modification of glycosylation sites of Env and selection of optimal protective epitopes might be useful for development of an effective vaccine against HIV/AIDS.

HIV-1 Vif Protein Mediates the Degradation of APOBEC3G in Fission Yeast When Over-expressed Using Codon Optimization

Interaction between the HIV-1 Vif protein and the cellular host APOBEC3G protein is a promising target for inhibition of HIV-1 replication. Considering that human cells are a very complicated environment for the study of protein interactions, the goal of this study was to check whether fission yeast could be used as a model cell for studying the Vif-APOBEC3G interaction. Vif and APOBEC3G were expressed in fusion with GFP protein in the S. pombe SP223 strain. Subcellular localizations of Vif and APOBEC3G were observed with fluorescent microscopy. Codon optimization was used to over express the Vif protein in S. pombe cells. The degradation of APOBEC3G mediated by Vif was tested through expressing Vif and GFP-APOBEC3G proteins in the same cell. Western Blot analysis was used to measure the corresponding protein levels under different experimental conditions. The results showed that the Vif protein was predominantly localized in the nucleus of S. pombe cells, APOBEC3G was localized in the cytoplasm and concentrated at punctate bodies that were often in close proximity to the nucleus but were not necessarily restricted from other regions in the cytoplasm. Vif protein expression levels were increased significantly by using codon optimization and APOBEC3G was degraded when Vif was over-expressed in the same S. pombe cells. These results indicate that fission yeast is a good model for studying the interaction between the Vif and APOBEC3G proteins.

PHASE-1 STUDIES OF MALARIOTHERAPY FOR HIV INFECTON

Objective. To determine whether malariotherapy (an old therapy for treatment of neurosyphilis) improves some clinical and laboratory parameters of HIV positive patients without iatrogenic complications. Methods. Total 8 asymptomatic HIV 1 positive subjects whose CD4 cell counts were over 250×10 6 cells/L were selected for the phase 1 studies of malariotherapy and were intravenously injected Plasmodia vivax to induce artificial malaria. Malaria was terminated with chloroquine after 10～20 malarial fever episodes. Cell bound CD4 levels were measured by APAAP (a solid phase enzyme essay) and levels of neopterin (NPT), beta 2 microglobulin (B2M), soluble tumor necrosis factor receptor 2(sTNF RII), interleukin 2(IL 2) and HIV P24 antigen were measured by ELISA. Patients were followed up to 24～30 months. Results.CD4 levels increased in 5, NPT decreased in 7 of 8 patients; IL 2 increased in 5 of 6 patients after malariotherapy. The total trends of B2M and sTNF RII basically remained stable. HIV P24 antigen remained undetectable in 6, remained detectably low level in 1 and experienced increase in 1 of 8 patients after malariotherapy. No any severe complications occurred in all 8 patients. Conclusions. The results indicate that malariotherapy basically is safe for HIV infection and it seems that the therapy improves some immunological parameters of HIV patients.

Comparison of the Immunogenicities of HIV-1 Mutants Based on Structural Modification of env

Eleven env mutants were designed and generated by site-directed mutagenesis of the regions around NAb epitopes and deletions of variable regions in env. The immunogenicities of the generated mutants were evaluated using single-cycle infection neutralization assays with two pseudoviruses and IFN-γ ELISPOT. Overall, five mutants (dWt, M2, M5-2, M5-1 and dM7) induced higher neutralization activities for both pseudoviruses than plasmid Wt, while only two of the mutants (dWt and M5-2) showed significant differences (P<0.05). Two mutants (M2 and dM2) induced more Env-specific T cells than plasmid Wt. Statistically however, significance was only reached for mutant M2. Thus, properly modified HIV-1 Env may have the potential to induce potent cellular and humoral immune responses.

HIV Vaccine-Challenges and Opportunities

The need for an efficacious HIV/AIDS vaccine remains the highest priority of the world HIV/AIDS agenda. The generation of an efficacious HIV/AIDS vaccine proves an enormous scientific challenge. This article reviews the neutralizing antibody problem,elusive immune protection,im-munogen design,pre-existing anti-vector immunity and design of phase 3 vaccine trials and the challenges and opportunities in development of HIV/AIDS vaccine are discussed.

Mechanisms of HIV envelope-induced T lymphocyte apoptosis

Infection by the human immunodeficiency virus （HIV） is characterized by a progressive depletion of CD4 T lymphocytes, which leads to dysfunction of the immune system. Although a variety of mechanisms may contribute to the gradual T cell decline that occurs in H/V-infected patients, abnormal apoptosis of infected or bystander T lymphocytes is an important event leading to immunodeficiency. The HIV envelope glycoprotein plays a crucial role in HIV associated apoptosis through both death receptor-mediated and mitochondria-dependent pathways. This review summarizes current knowledge of Env-mediated T lymphocyte apoptosis.

Acute hepatitis C in a chronically HIV-infected patient:Evolution of different viral genomic regions

AIM: To analyze the molecular evolution of different viral genomic regions of HCV in an acute HCV infected patient chronically infected with HIV through a 42-month follow-up.METHODS: Serum samples of a chronically HIV infected patient that seroconverted to anti HCV antibodies were sequenced, from the event of superinfection through a period of 17 months and in a late sample (42nd month). Hypervariable genomic regions of HIV (V3 loop of the gp120) and HCV (HVR-1 on the E2 glycoprotein gene) were studied. In order to analyze genomic regions involved in different biological functions and with the cellular immune response, HCV core and NS5A were also chosen to be sequenced. Amplification of the different regions was done by RT-PCR and directly sequenced. Confirmation of sequences was done on reamplified material. Nucleotide sequences of the different time points were aligned with CLUSTAL W 1.5, and the corresponding amino acid ones were deduced.RESULTS: Hypervariable genomic regions of both viruses (HVR1 and gp120 V3 loop) presented several nonsynonymous changes but, while in the gp120 V3 loop mutations were detected in the sample obtained right after HCV superinfection and maintained throughout, they occurred following a sequential and cumulative pattern in the HVR1. In the NS5A region of HCV, two amino acid changes were detected during the follow-up period, whereas the core region presented several amino acid replacements, once the HCV chronic infection had been established.CONCLUSION: During the HIV-HCV superinfection, each genomic region analyzed shows a different evolutionary pattem.Most of the nucleotide substitutions observed are nonsynonymous and clustered in previously described epitopes,thus suggesting an immune-driven evolutionary process.

The Role of HIV Replicative Fitness in Perinatal Transmission of HIV

Perinatal transmission of Human immunodeficiency virus(HIV),also called mother-to-child transmission(MTCT),accounts for 90% of infections in infants worldwide and occurs in 30%-45% of children born to untreated HIV-1 infected mothers.Among HIV-1 infected mothers,some viruses are transmitted from mothers to their infants while others are not.The relationship between virologic properties and the pathogenesis caused by HIV-1 remains unclear.Previous studies have demonstrated that one obvious source of selective pressure in the perinatal transmission of HIV-1 is maternal neutralizing antibodies.Recent studies have shown that viruses which are successfully transmitted to the child have growth advantages over those not transmitted,when those two viruses are grown together.Furthermore,the higher fitness is determined by the gp120 protein of the virus envelope.This suggests that the selective transmission of viruses with higher fitness occurred exclusively,regardless of transmission routes.There are many factors contributing to the selective transmission and HIV replicative fitness is an important one that should not be neglected.This review summarizes current knowledge of the role of HIV replicative fitness in HIV MTCT transmission and the determinants of viral fitness upon MTCT.

Animal models to study Mycobacterium tuberculosis and HIV co-infection

Mycobacterium tuberculosis(M.tb) and human immunodeficiency virus(HIV) co-infection has become a public health issue worldwide. Up to now, there have been many unresolved issues either in the clinical diagnosis and treatment of M.tb/HIV coinfection or in the basic understanding of the mechanisms for the impairments to the immune system by interactions of these two pathogens. One important reason for these unsolved issues is the lack of appropriate animal models for the study of M.tb/HIV coinfection. This paper reviews the recent development of research on the animal models of M.tb/HIV co-infection, with a focus on the non-human primate models.

Role of upper endoscopy in diagnosing opportunistic infections in human immunodeficiency virus-infected patients

Highly active antiretroviral therapy (HAART) has dramatically decreased opportunistic infections (OIs) in human immunodef iciency virus (HIV)-infected patients. However,gastrointestinal disease continues to account for a high proportion of presenting symptoms in these patients. Gastrointestinal symptoms in treated patients who respond to therapy are more likely to the result of drug-induced complications than OI. Endoscopic evaluation of the gastrointestinal tract remains a cornerstone of diagnosis,especially in patients with advanced immunodeficiency,who are at risk for OI. The peripheral blood CD4 lymphocyte count helps to predict the risk of an OI,with the highest risk seen in HIV-infected patients with low CD4 count (< 200 cells/mm3). This review provides an update of the role of endoscopy in diagnosing OI in the upper gastrointestinal tract in HIV-infected patients in the era of HAART.

Diagnostic value of antigenemia assay for cytomegalovirus gastrointestinal disease in immunocompromised patients

AIM:To investigate the utility of the cytomegalovirus(CMV)antigenemia assay for the diagnosis of CMV gastrointestinal disease(GID). METHODS:One hundred and thirty immunocompromised patients were enrolled in this study.Patients with a history of anti-CMV treatment and who had not undergone examination using the antigenemia assay were excluded.CMV-GID was defined as the detection of large cells with intranuclear inclusions alone or associated with granular cytoplasmic inclusions by biopsy.Biopsy sections were stained with hematoxylin and eosin and immunohistochemically stained with anti-CMV.We evaluated the association between CMV-GID and patient characteristics(symptoms,underlying disease,medication,leukocyte counts,and antigenemia assay).All patients were checked with an human immunodeficiency virus(HIV)antibody test before endoscopic examination.White blood cell(WBC)counts were obtained from medical records within 1 wk of endoscopy.Leukopenia was defined as a total WBC count<5000 cells/mm 3 . For HIV patients,we also checked CD4+counts from medical records. RESULTS:A total of 99 patients were retrospectively selected for analysis.Of the immunocompromised patients,19 had malignant disease,18 had autoimmune disease,19 had disorders of biochemical homeostasis, three had undergone transplantation,and 45 had HIV infection.A total of 50 patients had received immunosuppressive therapy.No patients had inflammatory bowel disease.Fifty-five patients were diagnosed as having CMV-GID.Univariate analysis indicated an association between HIV infection,leukopenia,and positive antigenemia and CMV-GID(P<0.05).Multivariate analysis using logistic regression revealed that HIV infection and positive antigenemia were the only independent factors related to CMV-GID(P<0.01).The sensitivity,specificity,positive predictive value,and negative predictive value of antigenemia for CMV-GID were 65.4%,93.6%, 91.9%,and 71.0%,respectively.In a subgroup analy-sis,patients with leukopenia displayed low sensitivity and high specificity.Minimal differences in accuracy were seen among patients with or without leukopenia. HIV-infected patients displayed low sensitivity and high specificity.Accuracy barely differed between HIV-positive and-negative patients.In HIV-infected patients, CD4 count<50 cells/μL resulted in low sensitivity and high specificity.Differences in accuracy among patients were minor,regardless of CD4 count.In patients who had undergone both quantitative real-time polymerase chain reaction(PCR)and antigenemia assay,real-time PCR was slightly more accurate in terms of sensitivity than the antigenemia assay;however,this difference was not statistically significant(P=0.312). CONCLUSION:If the antigenemia test is positive,endoscopic lesions are acceptable for the diagnosis of CMVGID without biopsy.The accuracy is not affected by HIV infection and leukopenia.Either PCR or the antigenemia assay are valid.

Primary Pleural Extranodal Non-Hodgkin＇s Lymphoma Presenting As Pleural Thickening-A Case Report

Primary pleural lymphoma is a rare entity that has been described in association with human immunodeficiency virus （HIV） infection or pyothorax. This paper reports on a 27 year old man with no history of HIV infection or pyothorax who presented with progressive dyspnea and heaviness of chest.Chest radiography revealed complete opacification of the left hemithorax, and contrast enhanced computed tomography showed large left pleural effusion and homogeneous, extensive thickening of the parietal pleura. CT guided biopsy of thickened pleura is suggestive of non-Hodgkin＇s lymphoma-T cell lymphoblastic variety. Physicians should be aware of this rare location of primary pleural lymphoma manifested by thickening of the pleura.

The Status of Human Immuno-deficiency Virus （HIV） Infection among Youth Aged 15-24 Years in Malawi and Kenya

HIV （Human Immuno-deficiency Virus） prevalence in Malawi is one of the highest in the world, with 10.3% of population living with HIV. Kenya has a prevalence rate of 6% and with 1.6 million people living with HIV infection. The broad objective of the study was to assess the proportion of youth aged 15-24 years affected by HIV in Malawi and Kenya. This was a descriptive study design. Data were mainly collected from reports from government, World Bank, World Health Organization and UN agencies. Graphs, tables and charts have been used to present statistics. Data for specific age cohort were hard to find and hence, data were used for general HIV and AIDS with special attention to the youth where possible. In Kenya, HIV prevalence among young women jumps three folds from 2.8% of 15-17 year olds to 8.3% among 23-24 year olds. In Malawi, around 2,100 young people and adolescents are infected with HIV every day. In 2013, four million young people aged 15-24 were living with HIV, with 29% aged under 19 years. This age group includes school going youths, newly employed, economically productive and sexually active group. HIV prevalence in Malawi has been declining over time among persons aged 15-19 years from 16.4% in 1999 to 11.8 % in 2004 to 10.6% in 2010 and 10.3% in 2016. However, in Kenya, the trend of HIV prevalence reached its peak of 10.55% in 1995-1996 after which it declined to 6.7% in 2003 and has been stable since then.

BED-CEIA估计HIV-1新近感染率的有效性及其影响因素的评价

在艾滋病流行病学研究中,衡量艾滋病流行趋势最常用的指标是HIV累积感染率和新近感染率.与累积感染率相比,新近感染率对艾滋病流行趋势预测、干预效果评价以及防制策略的制定等能提供更直接的信息.在获取新近感染率的方法中,除了经典的流行病学队列随访方法,目前普遍使用的血清学方法之一是IgG捕获BED酶联免疫法（BED-CEIA）.2001年,美国疾病预防控制中心（CDC）艾滋病免疫和诊断室评估了16种基于不同抗体和原理的HIV-1新近感染检测方法,发现新近感染者与既往感染者相比,各种抗体滴度均较低;其中gp41抗体滴度在新近感染者和既往感染者中的差别最大,两者的滴度区间几乎没有重叠,新近感染者的gp41抗体亲和力低于既往感染者,从而认为gp41抗体能够区分新近感染者和既往感染者,并且酶联免疫实验操作相对简单、效果也较理想,因此该室着手开发基于gp41抗体的HIV-1新近感染检测的酶联免疫方法[1].

Design and immunogenicity assessment of HIV-1 virus-like particles as a candidate vaccine

The rapid growth of the global HIV/AIDS epidemic makes it a high priority to develop an effective vaccine.Since a live attenuated or inactivated HIV vaccine is not likely to be approved for clinical application due to safety concerns,HIV virus like particles(VLPs) offer an attractive alternative because they are considered safer since they lack viral genome.We got a stable eukaryotic cell line by G418 resistance selection,engineered to express the HIV-1 structure protein Gag and Env efficiently and stably.We confirmed the presence of Gag and Env proteins in the cell culture supernatant and that they could self-assemble into VLPs.These VLPs were found to be able to elicit specific humoral and cellular immune response after immunization without any adjuvant.

Comment on the intervention of Traditional Chinese Medicine on survival rates of patients living with human immunodeficiency virus and acquired immune deficiency syndrome

Despite many differences between Traditional Chinese Medicine(TCM) and conventional medicine,the use of TCM in the treatment of human immunodeficiency virus and acquired immune deficiency syndrome(HIV/AIDS) is increasingly recognized and accepted by patients. Recent research findings on the benefits of Chinese herbal medicine on long-term survival in patients with HIV/AIDS are encouraging and hopeful, but inconclusive. More research is needed.