上海市人类免疫缺陷病毒阳性人群HIV-1分布特征分析

[目的 ]　分析上海市人类免疫缺陷病毒 (HIV )阳性人群HIV -1分布特征 ,为制定预防HIV传播措施提供科学依据。　 [方法 ]　选择 40例不同感染途径的HIV阳性者 ,提取其血浆中核酸进行扩增 ,然后进行序列测定 ,确定其HIV -1型别。　 [结果 ]　 3 8例分离到核酸的阳性者中 ,发现 4种HIV -1亚型 (A、B、B’和C)、2种重组亚型 (CRF0 1_AE和CRF0 8_BC)和 1种未见报道的亚型 (CRF0 1_AEenvBgagUpol)。不同人群感染毒株不同 ,经性接触传播感染者感染毒株较为广泛 ( 7种 ) ,而经血传播者都为B/B’亚型。　 [结论 ]　上海地区存在着多样的HIV -1亚型和重组毒株     

Molecular epidemiology of HIV-1 infection in Europe: An overview

Human Immunodeficiency Virus type 1 (HIV-1) is characterised by vast genetic diversity. Globally circulating HIV-1 viruses are classified into distinct phylogenetic strains (subtypes, sub-subtypes) and several recombinant forms. Here we describe the characteristics and evolution of European HIV-1 epidemic over time through a review of published literature and updated queries of existing HIV-1 sequence databases. HIV-1 in Western and Central Europe was introduced in the early-1980s in the form of subtype B, which is still the predominant clade. However, in Eastern Europe (Former Soviet Union (FSU) countries and Russia) the predominant strain, introduced into Ukraine in the mid-1990s, is subtype A (A_FSU) with transmission mostly occurring in People Who Inject Drugs (PWID). In recent years, the epidemic is evolving towards a complex tapestry with an increase in the prevalence of non-B subtypes and recombinants in Western and Central Europe. Non-B epidemics are mainly associated with immigrants, heterosexuals and females but more recently, non-B clades have also spread amongst groups where non-B strains were previously absent - non-immigrant European populations and amongst men having sex with men (MSM). In some countries, non-B clades have spread amongst the native population, for example subtype G in Portugal and subtype A in Greece, Albania and Cyprus. Romania provides a unique case where sub-subtype F1 has predominated throughout the epidemic. In contrast, HIV-1 epidemic in FSU countries remains more homogeneous with A_FSU clade predominating in all countries. The differences between the evolution of the Western epidemic and the Eastern epidemic may be attributable to differences in transmission risk behaviours, lifestyle and the patterns of human mobility. The study of HIV-1 epidemic diversity provides a useful tool by which we can understand the history of the pandemic in addition to allowing us to monitor the spread and growth of the epidemic over time.     

Non-human primates in HIV research: Achievements,limits and alternatives

An ideal model for HIV-1 research is still unavailable. However, infection of non-human primates (NHP), such as macaques, with Simian Immunodeficiency Virus (SIV) recapitulates most virological, immunological and clinical hallmarks of HIV infection in humans. It has become the most suitable model to study the mechanisms of transmission and physiopathology of HIV/AIDS. On the other hand, natural hosts of SIV, such as African green monkeys and sooty mangabeys that when infected do not progress to AIDS, represent an excellent model to elucidate the mechanisms involved in the capacity of controlling inflammation and disease progression. The use of NHP-SIV models has indeed enriched our knowledge in the fields of: i) viral transmission and viral reservoirs, ii) early immune responses, iii) host cell-virus interactions in tissues, iv) AIDS pathogenesis, v) virulence factors, vi) prevention and vii) drug development. The possibility to control many variables during experimental SIV infection, together with the resemblance between SIV and HIV infections, make the NHP model the most appropriate, so far, for HIV/AIDS research. Nonetheless, some limitations in using these models have to be considered. Alternative models for HIV/AIDS research, such as humanized mice and recombinant forms of HIV-SIV viruses (SHIV) for NHP infection, have been developed. The improvement of SHIV viruses that mimic even better the natural history of HIV infection and of humanized mice that develop a greater variety of human immune cell lineages, is ongoing. None of these models is perfect, but they allow contributing to the progress in managing or preventing HIV infection.     

抗HIV-1免疫基因的研究进展

人类免疫缺陷病毒1型(human immunodeficiency virus type 1,HIV -1)是艾滋病(Acquired Immune DeficiencySyndrome,AIDS)的病原体.HIV感染使人体免疫系统中最重要的CD4+T淋巴细胞减少,从而破坏人的免疫系统,最终使免疫系统崩溃,丧失对各种疾病的抵抗能力而并发多种感染和肿瘤最终导致死亡.宿主的一些抗艾滋病免疫基因如载脂蛋白B mRNA编辑酶催化多肽样蛋白3G、正常T细胞表达分泌的调节活化蛋白等在抑制HIV感染和延缓感染者疾病进展中都起着非常重要的作用.文章主要综述人体内抗HIV病毒的部分免疫基因及其作用机制.     

Screening of African sera stored for more than 17 years for HIV antibodies by site-directed serology

Antibodies to Human Immunodeficiency Virus type 1 (HIV-1) and type 2 (HIV-2) were investigated, using site-directed enzyme immunoassay (ELISA), in 320 specimens obtained from three remote, African tribes during 1969–1971. Using HIV-1 E34/E32 ELISA and HIV-2 149 ELISA, assays were conducted on 101 serum specimens from the Korekore tribe of Zimbabwe, 93 specimens from the Mano tribe of Liberia, and 126 specimens from the Turkana tribe of Kenya; specimens which tested positive in ELISA were further tested by radioimmunoprecipation assay (RIPA) and Western blot (WB). Two serum specimens from the Mano tribe of Liberia gave OD 492 nm values greater than 0.2 in HIV E34/E32 ELISA in all three runs. These two specimens reacted with HIV-1 envelope proteins gp160 and gp120 and the internal protein p24 in RIPA and WB; however, the reactivity was uncostant. All other serum specimens were negative for HIV-1 and HIV-2 antibodies. Site directed ELISA serology for HIV-1 and HIV-2 gave very low rates of false positive reactivity. Thus, reaction with HIV-1 antigen was identified in two persons of one tribe in Liberia in 1971, but HIV-2 antibodies were not detected in this tribe; HIV-1 and HIV-2 antibodies were absent during the late 1960's and early 1970's from two African tribes resident in Zimbabwe and Kenya.Corresponding author.     

Cross-subtype antibody and cellular immune responses induced by a polyvalent DNA prime-protein boost HIV-1 vaccine in healthy human volunteers

An optimally effective AIDS vaccine would likely require the induction of both neutralizing antibody and cell-mediated immune responses, which has proven difficult to obtain in previous clinical trials. Here we report on the induction of Human Immunodeficiency Virus Type-1 (HIV-1)-specific immune responses in healthy adult volunteers that received the multi-gene, polyvalent, DNA prime-protein boost HIV-1 vaccine formulation, DP6-001, in a Phase I clinical trial conducted in healthy adult volunteers of both genders. Robust cross-subtype HIV-1-specific T cell responses were detected in IFNgamma ELISPOT assays. Furthermore, we detected high titer serum antibody responses that recognized a wide range of primary HIV-1 Env antigens and also neutralized pseudotyped viruses that express the primary Env antigens from multiple HIV-1 subtypes. These findings demonstrate that the DNA prime-protein boost approach is an effective immunization method to elicit both humoral and cell-mediated immune responses in humans, and that a polyvalent Env formulation could generate broad immune responses against HIV-1 viruses with diverse genetic backgrounds.     

Hepatitis B and C Viruses Infections and Their Association with Human Immunodeficiency Virus: A Cross-Sectional Study among Blood Donors in Ethiopia

Background

Since the introduction of Highly Active Anti-Retroviral Therapy and the dramatic improvement in the prognosis of individuals with Human Immunodeficiency Virus, liver disease due to chronic viral hepatitis has become as important cause of morbidity and mortality in co-infected individuals. The objective of the study was to determine the Sero-prevalence of Hepatitis B Virus, Hepatitis C Virus and Human Immunodeficiency Virus and the association of the virus with Hepatitis B Virus and Hepatitis C Virus infection. As Human Immunodeficiency Virus and Hepatitis B Virus infections are highly prevalent and they are among the major public health concern in developing countries including Ethiopia investigating this problem is of paramount benefit. Although studies on co-infection of Hepatitis C Virus and Human Immunodeficiency Virus have clearly identified adverse effects of co-infection, the prevalence of Hepatitis C Virus infection and the association with Human Immunodeficiency Virus in developing countries including Ethiopia has not been know for sure.

Method

A cross sectional study was conducted from January 1 to 31, 2010, in Jimma University specialized hospital Blood Bank. The inclusion criteria of the study was adult who donated blood to Jimma University specialized hospital blood bank any time from establishment of the unit until January 2010 and whose record was retrieved. Accordingly 9,204 adults were included of which 6,063 were selected by lottery method. Data on socio-demographic variables (age and sex), laboratory test result for Hepatitis B surface Antigen, anti-Hepatitis C Virus antibody, anti-Human Immunodeficiency Virus 1 antibody, and Rapid Plasma Reagin tests were collected using structured questionnaire. After the data were collected, they were entered into a computer and analyzed using SPSS -16 for windows. P-Value of < 0.05 was taken to be statistically significant.

Results

The prevalence rate of Hepatitis B Virus, Hepatitis C Virus, Human Immunodeficiency Virus and syphilis infection were 2.1%, 0.2%, 2.1% and 0.7%, respectively. Sex and age had statistically significant association with Human Immunodeficiency and Hepatitis B virus infections where females were less likely to be infected. As age increases above 20 years, the risk of infection with Human Immunodeficiency Virus or Hepatitis B Virus increases. There was no association between Hepatitis B Virus, Hepatitis C Virus and Human Immunodeficiency Virus.

Conclusion

the prevalence rate of Hepatitis B Virus, Hepatitis C Virus and Human Immunodeficiency Virus infections among blood donors in Jimma University specialized hospital were lower as compared to previous studies, in addition there was no association between Hepatitis B Virus, Hepatitis C Virus and Human Immunodeficiency Virus. Thus, community based study should be conducted to confirm the relationship of Hepatitis B Virus, Hepatitis C Virus and Human Immunodeficiency Virus.     

Robust antigen-specific humoral immune responses to sublingually delivered adenoviral vectors encoding HIV-1 Env: association with mucoadhesion and efficient penetration of the sublingual barrier

The efficient induction of virus-specific mucosal antibodies is an important unmet objective in Human Immunodeficiency Virus Type-1 (HIV-1) vaccine research. One promising approach is sublingual (SL) immunization. We examined the effectiveness of SL delivery of two different viral vectors: (i) a recombinant adenovirus (rAd5), and (ii) a Herpes Simplex Virus Type-1 amplicon vector (HSV-1). Initial in vitro videomicroscopy experiments showed that rAd5 particles were trapped in saliva (i.e., that Ad5 was mucoadhesive) - unlike HSV-1 virions, which migrated freely in both saliva and water. In vivo imaging studies in mice revealed that only the rAd5 vector efficiently transduced the SL epithelium. Consistent with this, SL delivery of an rAd5 encoding HIV-1 envelope glycoprotein (Env) resulted in robust antigen-specific antibody responses in plasma and in vaginal washes, whereas SL delivery of a HSV-1 amplicon vector encoding HIV-1 Env failed to elicit Env-specific antibodies. In contrast, both vectors elicited equivalent humoral responses following intramuscular (IM) delivery. Finally, SL delivery of the rAd5:Env vector resulted in elevated levels of Env-specific serum IgA, and vaginal IgA and IgG, when compared to IM delivery of the same vector. These results findings shed light on vector properties (mucoadhesion, penetration of the sublingual barrier) which may be important for the induction of potent humoral immune responses following sublingual vector administration. Our data also show that SL delivery of an Env-encoding rAd5 vector can elicit a potent antigen-specific mucosal antibody response in the absence of adjuvant. Overall, these findings support the further exploration of the SL delivery route for HIV-1 vaccine delivery.     

Molecular typing of the recently expanding subtype B HIV-1 epidemic in Romania: evidence for local spread among MSMs in Bucharest area

HIV-1 subtype B is predominant in Europe except in some countries from Eastern Europe which are characterized by a high prevalence of non-B subtypes and circulating recombinant forms (CRFs). Romania is a particular case: the HIV-1 epidemic started with subtype F1 which is still the most prevalent. Previous studies have shown an increasing prevalence of subtype B which is the second most frequent one among the newly diagnosed individuals, followed by subtype C and several CRFs as well as unique recombinant forms (URFs). Our objective was to analyze in detail the characteristics (way of dispersal, association with transmission risk groups) of the subtype B infections in Romania by means of phylogenetic analysis. Among all the individuals sampled during 2003-2010, 71 out of 1127 patients (6.3%) have been identified to be infected with subtype B strains. The most frequent route of infection identified in HIV-1 subtype B patients in Romania was MSM transmission (39.6%), followed by the heterosexual route (35.2%). Many of the patients acquired the infection abroad, mainly in Western European countries. Phylogenetic analysis indicated the existence of a local transmission network (monophyletic clade) including 14 patients, mainly MSM living in the Bucharest area. We estimate the origin of the local transmission network that dates at the beginning of the 90s; the introduction of the F1 and C subtypes occurred earlier. The rest of the sequences were intermixed with reference strains sampled across Europe suggesting that single infection were not followed by subsequent dispersal within the local population. Although HIV-1 subtype B epidemic in Romania is recent, there is evidence for local spread among the MSMs, in addition to multiple introductions.     

Conformational constraints imposed on a pan-neutralizing HIV-1 antibody epitope result in increased antigenicity but not neutralizing response

2F5 is one of the few broadly neutralizing monoclonal antibodies against type 1 Human Immunodeficiency Virus (HIV-1). It recognizes the amino acid sequence ELDKWAS in gp41. We have previously identified a number of immunotargeting 2F5-reactive candidate immunogens. Three of them (designated H-BT1-3) have the ELDKWAS sequence constrained at beta-turn sites within the immunoglobulin heavy chain. Two others (L-CT and L-CTx3) have the sequence attached at the C-terminus of the immunoglobulin light chain with minimal conformational constraints. In the present investigation, the H-BTs were found to bind 2F5 with up to 10-fold higher affinities than their unconstrained counterpart. When used as immunogens, immunogen-specific antibodies were induced with or without adjuvant, confirming the immunotargeting potential of these immunogen constructs. While HIV-1 gp160 cross-reactive antibodies were induced, virus neutralization was not detected. Thus, factors other than 2F5 binding affinity may have a critical role to play in the design of a 2F5-based vaccine.     

SIV als Quelle von HIV

It is assumed that HIV, the human immunodeficiency virus, started its spread after the Second World War. Molecular analysis of the genome of various HIV-1 types has shown that this virus can be divided into the groups M, N, and O and that these genome sequences fit perfectly to the genomes found in SIV of chimpanzees (SIVcpz) living in the area of West and Central Africa. SIVcpz is nonpathogenic for chimpanzees indicating that the virus and host have adapted for a long period. HIV-2 genome sequences converge with SIV sequences of sooty mangabey monkeys from West Africa (SIVsm), covering the subtypes A to G from HIV-2. SIVsm is nonpathogenic for mangabey monkeys. All available data indicate that HIV-1 and HIV-2 have been introduced into humans at least several times. Since SIVcpz and SIVs from other monkeys are recombinant viruses, it cannot be excluded that a new recombinant SIV might again enter the human population and initiate a new epidemic.     

Update on the Human Immunodeficiency Virus

At the end of 2011, UNAIDS estimated that 34 million (31.4 to 35.9) individuals were infected by HIV worldwide and that 2.5 million were newly infected during the year. Since 2001, we have observed an increased number of HIV-infected patients in the world, due to an expanded access to antiretroviral drugs. More than 23,5 million (22.1 to 24.8) HIV-infected patients live in Sub-Saharan Africa. The number of HIV-infected patients in France is estimated at 152,000. Two types of HIV cause AIDS: HIV-1 and HIV-2 that are subdivided in groups (M, N, O, P for HIV-1; A to H for HIV-2), subtypes (A-D, F-H, J-K for HIV-1 group M), sub-subtype (A1-A4 for subtype A, F1 and F2 for subtype F in HIV-1 group M), circulating recombinant forms (CRF), and unique recombinant forms in a small number of patients. Virological diagnostic and monitoring techniques have been constantly upgraded since HIV-1 was isolated in 1983 and the first serological tests became available in 1985. This is especially true for HIV-1, the most prevalent worldwide.     

Detection and molecular characterization of Torque Teno Virus (TTV) in Uruguay

Torque Teno Virus (TTV), member of Anelloviridae family, is considered a worldwide distributed emergent virus and is currently classified into seven genogroups.Interestingly, the pathogenicity of TTV remains unclear. However, it has been constantly associated to hepatitis cases of unknown etiology (HUE) as well as extensively studied in concurrent infections with Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) and Human Immunodeficiency Virus type 1 (HIV-1).In South America, TTV epidemiological data is scant, involving some studies from Brazil, Venezuela, Colombia and Bolivia.The aim of this work was to investigate for the first time in Uruguay the presence of TTV by a nested-PCR system in 85 human serum samples infected with HBV and/or HCV and/or HIV-1 and in HUE cases.Overall, our results reported a TTV infection rate of 79% (67/85). Furthermore, the molecular characterization of Uruguayan strains revealed that one of them clustered in genogroup 1, while the remaining ones formed separate clusters closely related to genogroup 3, which should be confirmed by complete genome sequencing.Further investigation about TTV circulation in Uruguayan population is needed in order to provide additional information about the genetic variability and TTV epidemiology in South America.     

Dual and recombinant infections: an integral part of the HIV-1 epidemic in Brazil

We systematically evaluated multiple and recombinant infections in an HIV-infected population selected for vaccine trials. Seventy-nine HIV-1 infected persons in a clinical cohort study in Rio de Janeiro, Brazil, were evaluated for 1 year. A combination of molecular screening assays and DNA sequencing showed 3 dual infections (3.8%), 6 recombinant infections (7.6%), and 70 (88.6%) infections involving single viral subtypes. In the three dual infections, we identified HIV-1 subtypes F and B, F and D, and B and D; in contrast, the single and recombinant infections involved only HIV-1 subtypes B and F. The recombinants had five distinct B/F mosaic patterns: Bgag-p17/Bgag-p24/Fpol/Benv, Fgag-p17/Bgag-p24/Fpol/Fenv, Bgag-p17/B-Fgag-p24/Fpol/Fenv, Bgag-p17/B-Fgag-p24/Fpol/Benv, and Fgag-p17/B-Fgag-p24/Fpol/Fenv. No association was found between dual or recombinant infections and demographic or clinical variables. These findings indicate that dual and recombinant infections are emerging as an integral part of the HIV/AIDS epidemic in Brazil and emphasize the heterogenous character of epidemics emerging in countries where multiple viral subtypes coexist.     

Differential distribution of compound microsatellites in various Human Immunodeficiency Virus Type 1 complete genomes

Compound microsatellites consist of two or more individual microsatellites, and may originate from dynamic mutations or imperfection of microsatellites. Previous studies have found microsatellites were present in 81 completed Human Immunodeficiency Virus Type 1 (HIV-1) genomes, suggesting compound microsatellites may exist in viral genomes. However, up to now, compound microsatellites have not been analyzed in any viral genomes. We identified and characterized 238 compound microsatellites in 81 completed HIV-1 genomes. About 0-24.24% of all microsatellites could be categorized as compound microsatellites. Compound microsatellite distribution is very different in two aspects between diverse HIV-1 genomes. First, the number and motifs of compound microsatellites are variable between surveyed genomes. Second, the relative abundance and relative density of compound microsatellites exhibit very significant differences between these surveyed genomes, respectively. The relative abundance and relative density of compound microsatellites were weakly correlated with genome size and microsatellite density. We observed a more dynamic picture of compound microsatellites than previously reported in eukaryotes. This might be attributed to the lack of proofreading in HIV-1 genomes, as it has been demonstrated that the loss of polymerase proofreading activity can greatly enhance the mutation rate of microsatellites.     

Bayesian network analysis of resistance pathways against HIV-1 protease inhibitors

Interpretation of Human Immunodeficiency Virus 1 (HIV-1) genotypic drug resistance is still a major challenge in the follow-up of antiviral therapy in infected patients. Because of the high degree of HIV-1 natural variation, complex interactions and stochastic behaviour of evolution, the role of resistance mutations is in many cases not well understood. Using Bayesian network learning of HIV-1 sequence data from diverse subtypes (A, B, C, F and G), we could determine the specific role of many resistance mutations against the protease inhibitors (PIs) nelfinavir (NFV), indinavir (IDV), and saquinavir (SQV). Such networks visualize relationships between treatment, selection of resistance mutations and presence of polymorphisms in a graphical way. The analysis identified 30N, 88S, and 90M for nelfinavir, 90M for saquinavir, and 82A/T and 46I/L for indinavir as most probable major resistance mutations. Moreover we found striking similarities for the role of many mutations against all of these drugs. For example, for all three inhibitors, we found that the novel mutation 89I was minor and associated with mutations at positions 90 and 71. Bayesian network learning provides an autonomous method to gain insight in the role of resistance mutations and the influence of HIV-1 natural variation. We successfully applied the method to three protease inhibitors. The analysis shows differences with current knowledge especially concerning resistance development in several non-B subtypes.     

我国男男性行为人群艾滋病流行情况及HIV-1基因亚型特征

我国男男性行为(MSM)人群中艾滋病的发病率呈逐年上升趋势,需要引起社会重视.近年来,我国MSM人群中各种新HIV-1独特重组型(URFs)和流行重组型(CRFs)不断被发现,CRF01_AE和CRF07_BC已经成为我国主要的HIV-1流行亚型.及时发现和鉴定各种HIV-1亚型,对预防和控制艾滋病流行具有重大意义.     

Molecular typing of the local HIV-1 epidemic in Serbia

Worldwide HIV-1 pandemic is becoming increasingly complex, with growing heterogeneity of subtypes and recombinant viruses. Previous studies have documented HIV-1 subtype B as the predominant one in Serbia, with limited presence and genetic diversity of non B subtypes. In recent years, MSM transmission has become the most frequently reported risk for HIV infection among newly diagnosed patients in Serbia, but very little is known of the network structure and dynamics of viral transmission in this and other risk groups. To gain insight about the HIV-1 subtypes distribution pattern as well as characteristics of HIV-1 transmission clusters in Serbia, we analyzed the genetic diversity of the pol gene segment in 221 HIV-1-infected patients sampled during 2002–2011. Subtype B was found to still be the most prevalent one in Serbia, accounting for over 90% of samples, while greater diversity of other subtypes was found than previously reported, including subtypes G, C, A, F, CRF01 and CRF02. In total, 41.3% of analyzed subtype B sequences were found associated in transmission clusters/network, that are highly related with MSM transmission route.     

昆明市VCT人群中的HIV-1亚型和耐药基因型调查

摘要:目的　了解昆明市艾滋病自愿咨询检测（VCT）人群中的艾滋病病毒（HIV）的HIV-1亚型和耐药基因型分布情况。方法　于2013年11-12月在云南省疾病预防控制中心VCT门诊对就诊人群进行调查,并采样进行HIV抗体、CD4细胞、新发感染检测和HIV亚型和耐药基因型检测。结果　610例VCT样本中有96例为HIV抗体阳性（15.7%,96/610）,其中95例（99.0%,95/96）获得亚型分析结果,分别有CRF08_BC（40.0%,38/95）、CRF07_BC（27.4%,26/95）、CRF01_AE（27.4%,26/95）、C（4.2%,4/95）和B（1.1%,1/95）5种亚型。89例样本（92.7%,89/96）获得耐药基因型分析结果,有21例（23.6%,21/89）发生基因突变,有1例出现耐药传播突变位点（1.12％,1/89）。结论　VCT人群中的艾滋病病毒亚型以重组流行型为主,包括CRF08_BC、CRF07_BC和CRF01_AE。耐药毒株在该人群中为低流行。