艾滋病—1（HIV—1）的性传播

艾滋病—１（ＨＩＶ—１）的传播途径有性接触、血液接触和母婴传播,性传播是ＨＩＶ—１流行性传播的主要途径。ＨＩＶ—１经性接触传播占全球３３４０万ＨＩＶ—感染者的７５％以上。对ＨＩＶ—１的性传播的研究,为预防ＨＩＶ—１经性接触传播有重要意义。本文分析了Ｈ...     

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 …

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（ｐｅｒｉｐｈｅｒａｌ ｂｌｏｏｄ ｍｏｎｏｎｕｃｌｅａｒ ｃｅｌｌｓ,ＰＢＭＣ）中提取前病毒ＤＮＡ,分别使用ＨＩＶ－１和ＨＩＶ－２特异性引特用套式ＰＣＲ扩增ＨＩＶ－１和ＨＩＶ－２     

HIV感染检测技术的研究进展

ＨＩＶ感染的检测是防治艾滋病和控制其传播的重要手段。本文综述了从宿主标本中直接检测到病毒本身的ＰＣＲ技术的抗原检测,以及抗ＨＩＶ检测技术的应用情况及优缺点,并结合自己的工作实际对ＨＩＶ感染检测技术的选择使用进行评述     

巨噬细胞,细胞因子与人类免疫缺陷病毒感染的关系

目的研究认为在人类免疫缺陷病毒（ＨＩＶ）感染过程中除了ＣＤ４＾＋Ｔ细胞外,单核巨噬细胞是ＨＩＶ最易侵犯的目标。同时认为ＨＩＶ感染单核－巨噬细胞不仅受各种细胞因子的调节,而且ＨＩＶ的感染能影响因素的产生。本文重点介绍限ＨＩＶ感染单核－巨噬细胞的机制、体内外有关细胞因子产生的研究及各种细胞因子对ＨＩＶ表达的调节作用。通过细胞因子网络功能的研究,进一步阐明ＨＩＶ致病机制,并积极探索出治疗ＨＩＶ感染造成免     

HIV感染的基因治疗研究进展

由于目前尚无有效的抗ＨＩＶ感染的化学药物和疫苗,从九十年代开始,人们开始日益重视探索ＨＩＶ感染的基因治疗的新途径。ＨＩＶ感染的基因治疗就是把具有治疗作用的基因转移到合适的靶细胞中,使其在表达为ＲＮＡ或蛋白质后干扰ＨＩＶ基因表达及调控,以达到防治ＨＩＶ感染的目的。ＨＩＶ的分子生物学研究的深入和体细胞基因治疗技术的发展为ＨＩＶ感染的基因治疗提供了基础。目前采用的策略主要有三大类：抗病毒的基因治疗;细胞     

人类免疫缺陷病毒1型感染中的抗体中和反应

本文介绍了人类免疫缺陷病毒１型（ＨＩＶ－１）感染中有关中和抗体研究的新近进展,包括中和抗体反应的特异性,如中和表位的种类和表达,ＨＩＶ中和反应的机制等。地ＨＩＶ－１ｇｐ１２０和ｇｐ４１分子的研究结果资料,作了较为详尽的描述。文中尚提出了ＨＩＶ感染预防疫苗研制的途径。     

艾滋病发病机理研究中的十大热点问题

艾滋病发病机理研究中的十大热点问题宝福凯（昆明医学院基础部６５００３１）艾滋病是获得性兔疫缺陷综合征（ＡＩＤＳ）的音译，为ＨＩＶ感染的晚期表现。弄清ＡＩＤＳ发病机理的关键在于阐明ＡＩＤＳ发病前ＨＩＶ的感染过程和ＨＩＶ与宿主的相互作用。自首次报道ＡＩＤ...     

人工合成多肽检测抗HIV－1和HIV－2抗体的研究

采用固相法合成ＨＩＶ－１和ＨＩＶ－２两个多肽,建立了用混合多肽为包被抗原检测ＨＩＶ－１和ＨＩＶ－２感染的间接酶联免疫吸附法。检测４６份抗ＨＩＶ－１和ＨＩＶ－２抗体阳性血清标本以及９４份对照血清标本,与ＵＢＩ试剂比较,其阳性符合率为９７．８％,阴性符合率为１００％,总符合率为９９．３％。实验结果表明,此法可用于ＨＩＶ－１和ＨＩＶ－２感染的检测。     

庚型肝炎病毒NS5区蛋白鼠单克隆抗体的制备

庚型病毒性肝炎是近年来世界上才确认的一种新型肝炎［１～３］。庚型肝炎病毒（ＨＧＶ）呈世界性分布,经血液传播为主,也可母婴传播。ＨＧＶ容易形成持续性感染,类似ＨＩＶ和ＨＣＶ。据粗略估计,我国大约有１００万～１０００万ＨＧＶ携带者。因此,ＨＧＶ已成为继乙...     

HIV感染的辅助因子—融合素

ＨＩＶ感染的辅助因子——融合素黄仕和秦椿华（卫生部武汉生物制品研究所,武汉４３００６０）（同济医科大学工业毒理研究室,武汉４３００３０）关键词融合素ＨＩＶ感染１９８４年,研究者发现,ＨＩＶ感染细胞是通过细胞表面受体ＣＤ４进行的。二年后又发现,仅有ＣＤ...     

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.     

Risk factors for male to female transmission of HIV. European Study Group.

OBJECTIVE--To identify risk factors for sexual transmission of HIV from infected men to their female sexual partners. DESIGN--Cross sectional analysis as part of a continuing study. Data were obtained by interviewing heterosexual couples in which the man was infected with HIV. Risks were assessed by comparing couples in which transmission had occurred (woman infected with HIV) with those in which it had not (woman not infected) and estimated by independent odds ratios and their 95% confidence intervals. SETTING--Infectious disease and public health departments from nine centres in six European countries. PARTICIPANTS--153 Male index patients (mean age 30.4 years) and their 155 female partners (mean age 27.8 years). INTERVENTIONS--Women were tested to determine their HIV antibody state. Women with a risk of infection with HIV other than sexual contact with their infected partner were excluded. END POINT--Three risk factors for male to female transmission of HIV. MEASUREMENTS AND MAIN RESULTS--Three risk factors were identified: a history of sexually transmitted disease in the previous five years for the female partner (odds ratio 3.1, 95% confidence interval 1.1 to 8.6); index patient with full blown AIDS (5.4, 1.2 to 25.2); and practice of anal intercourse (5.8, 2.3 to 14.8). The proportion of women positive for HIV antibody was 27% (42/155), ranging from 7% (1 to 13%) (4/60) for couples with none of the three risk factors to 67% (45 to 89%) (12/18) for those with two or three of the risk factors. Duration of the relationship (median three years), frequency of sexual contacts, sexual practices other than anal intercourse, and contraceptive behaviour were not associated with infection of the partner. CONCLUSIONS--The risk of sexual transmission of HIV from an infected man to his female partner varies considerably according to the characteristics of the couple. The differences in rates of transmission in high risk groups may be considerably reduced if the risk factors are taken into account during individual and public health counselling.     

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 selectiv...     

Perinatal transmission of major, minor, and multiple maternal human immunodeficiency virus type 1 variants in utero and intrapartum

Previous studies have provided conflicting data on the presence of selective pressures in the transmission of a homogeneous maternal viral subpopulation to the infant. Therefore, the purpose of this study was to definitively characterize the human immunodeficiency virus type 1 (HIV-1) quasispecies transmitted in utero and intrapartum. HIV-1 envelope gene diversity from peripheral blood mononuclear cells and plasma was measured during gestation and at delivery in mothers who did and did not transmit HIV perinatally by using a DNA heteroduplex mobility assay. Children were defined as infected in utero or intrapartum based on the timing of the first detection of HIV. Untreated transmitting mothers (n = 19) had significantly lower HIV-1 quasispecies diversity at delivery than untreated nontransmittting mothers (n = 18) (median Shannon entropy, 0.711 [0.642 to 0.816] versus 0.853 [0.762 to 0.925], P = 0.005). Eight mothers transmitted a single major env variant to their infants in utero, and one mother transmitted a single major env variant intrapartum. Four mothers transmitted multiple HIV-1 env variants to their infants in utero, and two mothers transmitted multiple env variants intrapartum. The remaining six intrapartum- and two in utero-infected infants had a homogeneous HIV-1 env quasispecies which did not comigrate with their mothers' bands at their first positive time point. In conclusion, in utero transmitters were more likely to transmit single or multiple major maternal viral variants. In contrast, intrapartum transmitters were more likely to transmit minor HIV-1 variants. These data indicate that different selective pressures, depending on the timing of transmission, may be involved in determining the pattern of maternal HIV-1 variant transmission.     

Frequent detection of escape from cytotoxic T-lymphocyte recognition in perinatal human immunodeficiency virus (HIV) type 1 transmission: the ariel project for the prevention of transmission of HIV from mother to infant

Host immunologic factors, including human immunodeficiency virus (HIV)-specific cytotoxic T lymphocytes (CTL), are thought to contribute to the control of HIV type 1 (HIV-1) replication and thus delay disease progression in infected individuals. Host immunologic factors are also likely to influence perinatal transmission of HIV-1 from infected mother to infant. In this study, the potential role of CTL in modulating HIV-1 transmission from mother to infant was examined in 11 HIV-1-infected mothers, 3 of whom transmitted virus to their offspring. Frequencies of HIV-1-specific human leukocyte antigen class I-restricted CTL responses and viral epitope amino acid sequence variation were determined in the mothers and their infected infants. Maternal HIV-1-specific CTL clones were derived from each of the HIV-1-infected pregnant women. Amino acid substitutions within the targeted CTL epitopes were more frequently identified in transmitting mothers than in nontransmitting mothers, and immune escape from CTL recognition was detected in all three transmitting mothers but in only one of eight nontransmitting mothers. The majority of viral sequences obtained from the HIV-1-infected infant blood samples were susceptible to maternal CTL. These findings demonstrate that epitope amino acid sequence variation and escape from CTL recognition occur more frequently in mothers that transmit HIV-1 to their infants than in those who do not. However, the transmitted virus can be a CTL susceptible form, suggesting inadequate in vivo immune control.     

模拟HIV性传播特点的SIVmac239恒河猴直肠黏膜感染

目的制备SIVmac239恒河猴(Macaca mulatta)细胞适应株病毒,模拟HIV性传播感染特点进行恒河猴直肠黏膜感染研究,探索引起系统性感染的病毒阈值水平与机体病毒、免疫学之间相关性,为我国艾滋病黏膜疫苗等生物制剂有效性评价提供新的模型构建思路。方法参照HIV性传播自然感染剂量范围,选用SIVmac239连续升高的3种剂量直肠黏膜途径感染两只恒河猴,采取多种方法进行病毒血症和免疫反应特点分析。结果两只恒河猴经2×101TCID50和2×102TCID50病毒滴度2次攻击后45d,经检测均未建立系统性感染,病毒特异性免疫反应均为阴性;第3次2×103TCID50病毒滴度攻击后,M296猴表现出典型的系统性感染特点,并诱导特异性免疫反应。结论确认了HIV性传播过程中的病毒剂量效应关系,为预防性生物制剂的猴体有效性评价提供了新的思路。同时,发现SIVmac239Gag区特异性的T细胞免疫反应在病毒控制过程中发挥了关键作用,对于新一代艾滋病黏膜疫苗的抗原选择具有指导性意义。     

Live-cell real-time imaging reveals role of mitochondria in cell-to-cell transmission of HIV-1

We used live-cell, real-time fluorescence imaging of co-cultures of HIV-1 infected T cells and uninfected target cells to examine the action of mitochondria during cell-to-cell transmission of the virus. We find that mitochondria of HIV infected cells enter uninfected target cells and advance viral spread. We show that human mitochondria serve as viral reservoirs and carriers and that they can move between cells. This was confirmed by our results that purified mitochondria from HIV infected cells are infectious, and that mitochondrial inhibitors block HIV transmission. Viral infection and replication in the target cells were verified by syncytial formation and HIV-1 core protein p24 production. Our results offer new insights into the cellular mechanisms of viral transmission and identify mitochondria as new host targets for viral infection.     

Mother-to-infant transmission of SIV via breast-feeding in rhesus macaques

To decipher the mechanisms involved in oral transmission of human immunodeficiency virus/simian immunodeficiency virus (HIV/SIV) through breast-feeding, we have developed an animal model using SIV-infected lactating rhesus macaques (Macaca mulatta) and their infants. Five of eight macaque infants became infected during a 10-month study course after SIV inoculation of lactating dams. In a second study, three of four chronically infected female macaques transmitted virus to their infants through breast-feeding within 4 months of birth. Transmission of virus to infants did not correlate with viral loads in either milk or plasma. Infants were infected with homogeneous virus populations, while milk samples near the time of transmission were more diverse. These studies suggest that specific viral phenotypes are selectively transmitted through breast-feeding.     

The integrated HIV-1 provirus in patient sperm chromosome and its transfer into the early embryo by fertilization

Complete understanding of the route of HIV-1 transmission is an important prerequisite for curbing the HIV/AIDS pandemic. So far, the known routes of HIV-1 transmission include sexual contact, needle sharing, puncture, transfusion and mother-to-child transmission. Whether HIV can be vertically transmitted from human sperm to embryo by fertilization is largely undetermined. Direct research on embryo derived from infected human sperm and healthy human ova have been difficult because of ethical issues and problems in the collection of ova. However, the use of inter-specific in vitro fertilization (IVF) between human sperm and hamster ova can avoid both of these problems. Combined with molecular, cytogenetical and immunological techniques such as the preparation of human sperm chromosomes, fluorescent in situ hybridization (FISH), and immunofluorescence assay (IFA), this study mainly explored whether any integrated HIV provirus were present in the chromosomes of infected patients' sperm, and whether that provirus could be transferred into early embryos by fertilization and maintain its function of replication and expression. Evidence showed that HIV-1 nucleic acid was present in the spermatozoa of HIV/AIDS patients, that HIV-1 provirus is present on the patient sperm chromosome, that the integrated provirus could be transferred into early embryo chromosomally integrated by fertilization, and that it could replicate alongside the embryonic genome and subsequently express its protein in the embryo. These findings indicate the possibility of vertical transmission of HIV-1 from the sperm genome to the embryonic genome by fertilization. This study also offers a platform for the research into this new mode of transmission for other viruses, especially sexually transmitted viruses.     

Characterization of human immunodeficiency virus type 1 (HIV-1) envelope variation and neutralizing antibody responses during transmission of HIV-1 subtype B

We analyzed neutralization sensitivity and genetic variation of transmitted subtype B human immunodeficiency virus type 1 (HIV-1) in eight recently infected men who have sex with men and the virus from the six subjects who infected them. In contrast to reports of heterosexual transmission of subtype C HIV-1, in which the transmitted virus appears to be more neutralization sensitive, we demonstrate that in our study population, relatively few phenotypic changes in neutralization sensitivity or genotypic changes in envelope occurred during transmission of subtype B HIV-1. We suggest that limited genetic variation within the infecting host reduces the likelihood of selective transmission of neutralization-sensitive HIV.