In Vitro Modification of Human Immunodeficiency Virus Type 1 (HIV-1) Infectivity by the U937 Cells

The effect of host cell factors on infectivity of human immunodeficiency virus type 1 (HIV-1) was studied by infecting a monoblastoid cell line (U937) or a T-cell line (MOLT-4) with a highly infective single clone of HIV-1 and comparing the infectivity of the produced viruses to different cell lines. Chronically infected U937 cells consistently produced viruses with minimal infectivity. This phenotypic change was host-dependent as the back-passage of the U937-produced low infective viruses into MOLT-4 cells resulted in regaining their original high infectivity. Southern and Northern blot analyses of the HIV-1 grown in U937 cells did not reveal any genomic difference between it and the virus grown it MOLT-4 cells. The radioimmunoprecipitation analysis of viral proteins showed that the HIV-1-infected U937 cells had a different pattern of envelope glycoproteins and core proteins, which well correlated with the low infectivity of the produced viruses. This experimental system using MOLT-4 and U937 cell lines would be useful to further explore host cell factor(s) which play an important role in the regulation of HIV-1 infectivity.     

HIV(+)/AIDS并发肺结核与单纯肺结核患者临床对照分析

提高对HIV(+)/AIDS并发肺结核临床表现的认识。方法:选取1998年以来我院收治的HIV(+)/AIDS并发肺结核的病例共47例为观察组(A组),及同期住院的HIV(-)单纯肺结核病例50例为对照组(B组)进行回顾性对照分析。结果:(1)A组发烧和体重下降较B组更常见,而咳嗽和咯血较B组少见;(2)A组痰抗酸杆菌阳性率显著低于B组;(3)A组结核杆菌培养阳性率显著低于B组,而耐多药结核(MDR-TB)所占比率显著高于B组;(4)肺结核的X线表现为弥漫性浸润或粟粒性阴影的,A组多于B组,而A组影像学空洞率显著低于B组;(5)A组合并肺外结核较B组多见,A组淋巴系统较B组常发生结核病变,A组全身血液播散性结核病的发病率明显高于B组;(6)PPD结核菌素反应阳性率A组显著低于B组,A组PPD阳性率与外周CD4+T淋巴细胞数相关。结论:HIV(+)/AIDS患者并发肺结核临床表现不典型。     

HIV and Latino migrant workers in the USA

Abstract

Migrant workers from Latin America are an essential source of economic development in the US agricultural industry. A majority of migrants are from Mexico and are undocumented and they represent a vulnerable and marginalized group in American society. There is a growing concern for HIV disease in the migrant community. The HIV prevalence rate among migrants is higher than the average rates in USA and in countries of Latin America. There are many behavioural, social, cultural, and health care risk factors and barriers that place migrants at increased risk for HIV infection. Many migrant workers contract HIV while working and living in the USA, which has contributed to rising HIV infection rates in Mexico. In order to prevent an increasing epidemic of HIV disease in Latino migrant workers, there is an urgent call for new and improved health care policies at the international, federal, state, and local levels.     

On transient effects in the HIV/AIDS epidemic

During the initially exponential spread of the human immunodeficiency virus (HIV—the causative agent of AIDS) the growth rate of the number of AIDS cases decreases from plus infinity to the growth rate of HIV infections. A sensitivity analysis shows that for all reasonable values of the parameters of the HIV epidemic (incubation period, initial doubling time, etc.) the effect of this positive transient becomes negligible when the annual number of AIDS cases reaches a few dozen. Necessary and sufficient conditions are given for the growth rate of the number of AIDS cases to be monotonically decreasing during the positive transient. A mildly pathological density function for the incubation period of AIDS provides an example of a growth rate of AIDS that does not decrease monotonically, even though HIV is spreading exponentially. A negative transient occurs when the growth rate of HIV begins to decrease. In this context a somewhat surprising result emerges under the assumption that the growth rate of HIV is non-increasing: the growth rate of AIDS is at all times larger than the growth rate of HIV. A logistic HIV epidemic illustrates this result, and implications for the growth of the HIV epidemic in the United States and Europe are discussed. In particular, it is shown that the positive transient must have passed by 1982 in the United States and by 1986 or 1987 for the five European countries with the largest caseloads.     

Granulocyte-Macrophage Colony-Stimulating Factor and Tumor Necrosis Factor Alpha in Patients with Human Immunodeficiency Virus (HIV) Type 1 Infection

Variations in cytokine production in patients with human immunodeficiency virus (HIV) infection could be involved in the physiopathology and in the progression of the disease. Therefore we studied the level of granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor α (TNFα) produced in patients with HIV infection at stage II (asymptomatic seropositives) and stage IV (AIDS) of the CDC classification, by using an enzyme amplified sensitivity immunoassay. We measured the level of GM-CSF and TNFα in supernatant of phytohemagglutinin-activated peripheral blood mononuclear cells from patients and healthy individuals. In one out of 10 stage II patients and 4 out of 14 stage IV patients, we obtained higher levels of GM-CSF than the mean + 2 S.D. of controls, but in 3 stage IV patients with very low CD4+ T lymphocyte counts (< 50/mm^–3) compared to other patients, the GM-CSF values were very low. High levels of TNFα were detected in 3 out of 10 stage II and 6 out of 11 stage IV patients. The high values of TNFα were associated with high values of GM-CSF in stage II and in most of AIDS patients except those with very low CD4⁺ T cell counts, who produced low levels of GM-CSF. Plasma levels of cytokines were evaluated in 10 stage II, 22 stage IV patients and 20 controls. Increased levels of GM-CSF (more than 9 pg/ml) were observed in the plasma from 8 out of 10 stage II patients and 17 out of 22 stage IV patients. The tendency that increased levels of GM-CSF were associated with increased levels of TNFα was observed in plasma from stage IV patients. We report a disarray of GM-CSF production in patients with HIV infection that could be involved in clinical manifestations and progression of the disease.     

A modeled time-varying density function for the incubation period of AIDS

Building on the Weibull distribution, we develop a modeled time-varying density function of the incubation time between exposure to HIV infection and full-blown AIDS. This approach leads to a series of cohort-specific density functions that take into account the increasing impact of new therapies such as zidovudine (AZT). The resulting modeled density functions are studied in detail, particularly with regard to their modes and medians. The mode is sensitive to changes in the period incubation time distribution, with even a possibility of a bimodal distribution for certain combinations of the parameters that determine the rate at which the period median incubation time changes. An important substantive result is that when a period median incubation period slowly increases to some leveling off value, say m(x _c ), then it is surprisingly early on that cohorts of infected individuals have a median incubation period very close to that ultimate value m(x _c ).     

HIV and HCV： from Co-infection to Epidemiology, Transmission, Pathogenesis, and Treatment

Human immunodeficiency virus (HIV) is the infectious agent causing acquired immu-nodeficiency syndrome (AIDS),a deadliest scourge of human society. Hepatitis C virus (HCV) is a major causative agent of chronic liver disease and infects an estimated 170 million people worldwide,resulting in a serious public health burden. Due to shared routes of transmission,co-infection with HIV and HCV has become common among individuals who had high risks of blood exposures. Among hemophiliacs the co-infection rate accounts for 85%; while among injection drug users (IDU) the rate can be as high as 90%. HIV can accelerate the progression of HCV-related liver disease,particularly when immunodeficiency has developed. Although the effect of HCV on HIV infection is controversial,most studies showed an increase in mortality due to liver disease. HCV may act as a direct cofactor to fasten the progression of AIDS and decrease the tolerance of highly active antiretroviral therapy (HARRT). Conversely,HAART-related hepatotoxicity may enhance the progression of liver fibrosis. Due to above complications,co-infection with HCV and HIV-1 has imposed a critical challenge in the management of these patients. In this review,we focus on the epidemiology and transmission of HIV and HCV,the impact of the two viruses on each other,and their treatment.     

HIV and HCV: from Co-infection to epidemiology, transmission, pathogenesis, and treatment

Human immunodeficiency virus (HIV) is the infectious agent causing acquired immunodeficiency syndrome (AIDS), a deadliest scourge of human society. Hepatitis C virus (HCV) is a major causative agent of chronic liver disease and infects an estimated 170 million people worldwide, resulting in a serious public health burden. Due to shared routes of transmission, co-infection with HIV and HCV has become common among individuals who had high risks of blood exposures. Among hemophiliacs the co-infection rate accounts for 85%; while among injection drug users (IDU) the rate can be as high as 90%. HIV can accelerate the progression of HCV-related liver disease, particularly when immunodeficiency has developed. Although the effect of HCV on HIV infection is controversial, most studies showed an increase in mortality due to liver disease. HCV may act as a direct cofactor to fasten the progression of AIDS and decrease the tolerance of highly active antiretroviral therapy (HARRT). Conversely, HAART-related hepatotoxicity may enhance the progression of liver fibrosis. Due to above complications, co-infection with HCV and HIV-1 has imposed a critical challenge in the management of these patients. In this review, we focus on the epidemiology and transmission of HIV and HCV, the impact of the two viruses on each other, and their treatment.      

Extracellular HIV-1 Nef increases migration of monocytes

Infiltration of human immunodeficiency virus type 1 (HIV-1)-infected and uninfected monocytes/macrophages in organs and tissues is a general phenomenon observed in progression of acquired immunodeficiency syndrome (AIDS). HIV-1 protein Nef is considered as a progression factor in AIDS, and is released from HIV-1-infected cells. Here, we show that extracellular Nef increases migration of monocytes. This effect is (i) concentration-dependent, (ii) reaches the order of magnitude of that induced by formyl-methyonyl-leucyl-proline (fMLP) or CC chemokine ligand 2 (CCL2)/monocyte chemotactic protein (MCP)-1, (iii) inhibited by anti-Nef monoclonal antibodies as well as by heating, and (iv) depends on a concentration gradient of Nef. Further, Nef does not elicit monocytic THP-1 cells to express chemokines such as CCL2, macrophage inhibitory protein-1alpha (CCL3) and macrophage inhibitory protein-1beta (CCL4). These data suggest that extracellular Nef may contribute to disease progression as well as HIV-1 spreading through affecting migration of monocytes.     

嵌合人/牛免疫缺陷病毒cDNA(pHBIV-2)传染性克隆的构建及其生物学活性

为探讨牛免疫缺陷病毒(BIV)Tat能否在功能上取代HIV Tat,构建用BIV tat取代HIV tat的嵌合人/牛免疫缺陷病毒(pHBIV-2)cDNA,将其转染人源MT4细胞.PCR、RT-PCR法检测到嵌合基因组在MT4细胞中可稳定地存在并转录;套式Alu-PCR法检测到嵌合基因组可整合到细胞基因组中;RTase活性测定及IFA检测显示,嵌合基因在MT4细胞中得到了翻译.结果表明,HIV的tat基因用BIVtat取代后产生的传染性cDNA克隆,仍能在人源MT4细胞中产生有复制性的重组病毒.     

猴免疫缺陷病毒（SIV）猴模型的建立

应用ＳＩＶｍａｃ毒株感染中国恒河猴１３只,感染剂量为病毒液的１０－１～２×１０－５;感染食蟹猴４只,感染剂量为１０－２。感染后２周出现各种症状和体征如皮疹,浅表淋巴结肿大,脾肿大,血象白细胞总数下降,出现异常淋巴细胞和中性白细胞。感染后期Ｔ４下降,Ｔ４、Ｔ８比例倒置等。从外周血淋巴细胞和血浆分离病毒阳性,血清抗体上升。淋巴结组织切片呈规律性改变,即淋巴滤泡增生－滤泡耗竭－淋巴组织耗竭或逐渐恢复。感染后２．５个月有急性死亡病例,以后呈散在死亡例,尸检还发现机遇性感染如肺寄生虫,肺、肝巨细胞病毒感染等。     

替换HIV-1衣壳蛋白基因SHIV的构建及其活性测定

将猴免疫缺陷病毒(Simianimmunodeficiencyvirus,SIVmm239)中gag基因的衣壳蛋白部分置换成人免疫缺陷病毒(Humanimmunodeficiencyvirustype1,HIV-1HXBc2)的相应部分,构建出替换了衣壳蛋白基因的人/猿嵌合免疫缺陷病毒(SHIV)原病毒DNA。用此SHIV原病毒DNA转染293T细胞,细胞中能够检测到嵌合病毒基因的转录与翻译;在细胞培养液上清中亦可检测到装配出的病毒颗粒。病毒颗粒形态正常,含有基因组RNA,具有反转录酶活性,嵌合的外源衣壳蛋白能够正确剪切,形成棒状的核心。将此嵌合SHIV病毒感染MT4细胞,病毒能够吸附并进入细胞,能完成反转录过程,但不能增殖。     

Rates of amino acid change in the envelope protein correlate with pathogenicity of primate lentiviruses

A spectrum of pathogenicity has been observed for primate lentiviruses in their natural hosts. For example, human immunodeficiency virus type 1 (HIV-1) is a potent etiologic agent for AIDS in man, whereas there is no evidence to date which indicates that simian immunodeficiency virus from African green monkeys (SIVAGM) causes immunodeficiency in AGM. We measured the relative rates of amino acid change, as the ratio of the number of nonsynonymous to synonymous (silent) nucleotide substitutions, for six primate lentiviruses evolving in their respective hosts. These rates for the external envelope glycoprotein (gp120) and gag coding sequences are 2–3 times higher for pathogenic HIV-1 and SIV..ac (macaque) than for minimally pathogenic SIVAGM and SIVsn,m (sooty mangabey), and intermediate for HIV-2. We speculate that the increased rates of nonsynonymous changes in gp120 and gag coding sequences are due to viral escape from immune surveillance and are indicative of higher immunogenicity of these proteins in their hosts. Based on these results and available experimental data, we conclude that there is a positive correlation between lentiviral pathogenicity and immunogenicity of the Env and Gag proteins in a given host. This hypothesis is consistent with recent data suggesting that immune system activation or autoimmunity induced by viral antigens may be important in the pathogenesis of AIDS.Correspondence to: E.G. Shpaer     

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...     

The T-cell receptor Vβ repertoire in naive and human immunodeficiency virus-1 (HIV-1) infected chimpanzees

Using a panel of human T-cell receptor (TCR) variable region β chain (Vβ) polymerase chain reaction (PCR) primers, we performed cross-sectional and longitudinal analyses of the TCR Vβ repertoire in naive and HIV-1 infected chimpanzees. We demonstrate that our TCR PCR primer panel will support amplification of chimpanzee cDNA from most of the TCR Vβ families. However, no differences in TCR Vβ expression were found between the naive and HIV-1 infected chimpanzees, unlike the TCR Vβ repertoire perturbation found in HIV-1 infected human subjects. This finding suggests that a complete TCR repertoire in HIV-1 infected chimpanzees is associated with the maintenance CD4 + T-cell numbers and lack of progression to AIDS.     

人免疫缺陷病毒/艾滋病细胞免疫疫苗研究进展

由于人免疫缺陷病毒(HIV)具有变异快、亚型多、攻击免疫系统等特殊的生物学特点,HIV/艾滋病疫苗至今尚未研制成功。20多年来,艾滋病疫苗研究主要采用中和抗体为主和细胞免疫为主等两种策略,然而目前仍没有实质性突破。诱发广谱有效的强CD8+T细胞反应是研制有效HIV疫苗的重要策略。以次要保护性抗原为靶抗原、优化目的基因表达、多抗原联合使用策略,为研究HIV细胞免疫疫苗引入了新的思路。综合分析这些进展,对于重新思考艾滋病疫苗的研究策略可能会有所帮助。     

Relative contribution of free-virus and synaptic transmission to the spread of HIV-1 through target cell populations

Human immunodeficiency virus can spread through target cells by transmission of cell-free virus or directly from cell-to-cell via formation of virological synapses. Although cell-to-cell transmission has been described as much more efficient than cell-free infection, the relative contribution of the two transmission pathways to virus growth during multiple rounds of replication remains poorly defined. Here, we fit a mathematical model to previously published and newly generated in vitro data, and determine that free-virus and synaptic transmission contribute approximately equally to the growth of the virus population.