Superinfection of a chimpanzee with a second strain of human immunodeficiency virus.

Two chimpanzees, one (C-499) infected with the acquired immunodeficiency syndrome-associated retrovirus type 2 (ARV-2) strain of human immunodeficiency virus (HIV) and one (C-560) infected with the lymphadenopathy-associated virus type 1 (LAV-1) strain of HIV, were inoculated with approximately 10(4) tissue culture infective doses of the reciprocal strain. At the time of the second inoculation, both chimpanzees had high titers of HIV-specific antibodies, including antibodies that neutralized both virus strains. After inoculation of the second strain of HIV, the antibody titers in both chimpanzees increased 4- to 10-fold, and in one chimpanzee (C-499), the numbers of infectious peripheral blood mononuclear cells (PBMC) increased 1,000-fold to levels that are comparable with those observed after primary HIV infections. By restriction enzyme analysis of virus recovered from PBMC, both ARV-2 and LAV-1 were identified in C-499, thus demonstrating that superinfection had occurred.     

HIVcleave: a web-server for predicting human immunodeficiency virus protease cleavage sites in proteins

According to the 'distorted key theory' [K.C. Chou, Analytical Biochemistry, 233 (1996) 1-14], the information of cleavage sites of proteins by HIV (human immunodeficiency virus) protease is very useful for finding effective inhibitors against HIV, the culprit of AIDS (acquired immunodeficiency syndrome). To meet the increasing need in this regard, a web-server called HIVcleave was established at http://chou.med.harvard.edu/bioinf/HIV/. In this note we provide a step-to-step guide for how to use HIVcleave to identify the cleavage sites of a query protein sequence by HIV-1 and HIV-2 proteases, respectively.     

Production of Stable Cell Lines on the Basis of the Cultured RPMI 8866 B-Cells with Constant and Inducible Expression of the Human Immunodeficiency Virus Tat Protein

Russian Journal of Developmental Biology - Highly-efficient antiretroviral therapy allows controlling human immunodeficiency virus (HIV) and preventing the development of immunodeficiency. However,...     

Derivation and characterization of a highly pathogenic isolate of human immunodeficiency virus type 2 that causes rapid CD4+ cell depletion in Macaca nemestrina

With few exceptions, humans are the only species known to develop acquired immunodeficiency syndrome (AIDS) after human immunodeficiency virus (HIV) infection. We report here that an isolate of HIV type 2, EHO, readily established persistent infection in 100% of Macaca nemestrina in three consecutive transmission studies. Of the eight infected animals, five showed persistently high virus load and six developed AIDS-like diseases or CD4+ cell depletion within 4 years of infection. The pathology and clinical signs closely parallel those of HIV-1 infection of humans, including lymphadenopathy, anemia, CD4+ cell depletion, and opportunistic infections. A cell-free virus stock was established from the lymph nodes of an animal that developed AIDS-like diseases. This virus, HIV-2/287, was highly pathogenic in M. nemestrina, causing CD4+ cell depletion within 2-8 weeks postinfection. While both HIV-2 EHO and HIV-2/287 use predominantly CXCR4, the latter shows greatly enhanced replicative capacity in macaque peripheral blood mononuclear cells (PBMCs). The establishment of a human immunodeficiency virus that causes rapid and reproducible CD4 cell depletion in macaques could facilitate the study of HIV pathogenesis and the development of effective vaccines and therapy against AIDS.     

Seroprevalence of herpes simplex virus type 2 in adult HIV-infected patients and blood donors in Croatia

The present study estimates herpes simplex virus type 2 (HSV-2) seroprevalence and evaluates its association with age, sex, human herpesvirus type 8 (HHV-8) and human immunodeficiency virus (HIV) among adults in Croatia. A cross-sectional survey included 166 HIV-infected patients and 219 blood donors. Antibodies against HSV-2 were determined by enzyme immunoassays based on gG2 recombinant glycoprotein. HSV-2 seroprevalence was 45.8% in HIV-infected patients and 8.7% in blood donors (p < 0.0001; OR 8.8; 95% CI 5.05-15.49). Independent predictors of HSV-2 seropositivity were HIV infection (OR 11.0; 95% CI 5.93-20.41), female gender (OR 2.28; 95% CI 1.22-4.26), older age (OR 3.93; 95% CI 2.74-7.11), and HHV-8 seropositivity (OR 2.72; 95% CI 1.09-6.75). Understanding the epidemiology of HSV-2 is a critical first step in designing interventions to decrease HSV-2 and HIV transmission. The association of HSV-2 with HIV infection and HHV-8 antibodies suggests a similar transmission route.     

Synthesis and Anti-HIV Activity of Novel 2′-Deoxy-2′-β-Fluoro-Threosyl Nucleoside Phosphonic Acid Analogues

Novel 2′-deoxy-2′-β-fluoro-threose purine phosphonic acid analogues were designed and racemically synthesized from 2-propanone-1,3-diacetate. Condensation successfully proceeded from a glycosyl donor 9 under Vorbrüggen conditions. Cross-metathesis of vinyl analogues 13 and 23 with diethyl vinylphosphonate yielded the desired nucleoside phosphonate analogues 14 and 24, respectively. Ammonolysis and hydrolysis of phosphonates yielded the nucleoside phosphonic acid analogues 16, 19, 26, and 29. The synthesized nucleoside analogues were subjected to antiviral screening against human immunodeficiency virus (HIV)-1. Adenine analogue 18 exhibited weak in vitro activities against human immunodeficiency virus (HIV)-1.     

Synthesis of N-Glycosylated Pyridines as New Antiviral Agents

Abstract

A series of 3-cyanopyridine glycosides have been synthesized and evaluated for their inhibitory activity against human immunodeficiency virus (HIV) replication in MT-4 cells. Among the 3-cyanopyridine glycosides 6-(p-methylphenyl) and 6-(p-aminophenyl) were the most selective inhibitors of HIV replication.     

基于调控趋化性细胞因子受体CCR5抗HIV-1的研究进展

获得性免疫缺陷综合征(AIDS),又称"艾滋病",是威胁着人类生命健康的重大传染性疾病。趋化性细胞因子受体5(Chemotactic cytokine receptor 5,CCR5)作为嗜巨噬细胞性1型人类免疫缺陷病毒(Human immunodeficiency virus type 1,HIV-1)进入宿主细胞的必需的辅助受体自发现以来被广泛关注。CCR5在HIV靶细胞表面的表达水平与靶细胞的病毒载量呈正相关且和艾滋病的进程强相关。因此,通过干预CCR5在靶细胞表面的表达能在一定程度上阻止HIV进入靶细胞。因此,本文从分子水平阐述干预CCR5的主要生物学机制,并对近几年的研究进行综述。     

Cross-reactive cytotoxic T lymphocytes against human immunodeficiency virus type 1 protease and gamma interferon-inducible protein 30

The gamma interferon (IFN-gamma)-inducible protein 30 (IP-30) signal peptide -11 to -3 (LLDVPTAAV) is a prominent self peptide expressed with the class I human histocompatibility leukocyte antigen A2 (HLA-A2). Stimulation of peripheral blood mononuclear cells (PBMC) from HLA-A2 human immunodeficiency virus type 1 (HIV-1)-infected individuals with an HLA-A2-restricted HIV protease (PR) peptide 76-84 (LVGPTPVNI) activated cytotoxic T lymphocytes (CTL) against the IP-30 signal peptide. Since HIV-1 PR 76-84 stimulated CD8+ T cells from these individuals to secrete IFN-gamma, we tested whether the activation of IP-30-specific CTL in vitro resulted from T-cell cross-reactivity or from up-regulation of IP-30 by IFN-gamma. Neither high levels of exogenous IFN-gamma nor incubation of PBMC with other HIV peptides triggering substantial IFN-gamma release activated IP-30-specific CTL. Although the IP-30 signal peptide did not stimulate IFN-gamma release from freshly isolated PBMC, it activated CTL in vitro against itself and HIV PR 76-84. Peptide-stimulated IFN-gamma release, cold target inhibition, and HLA-A2/immunoglobulin dimer-mediated binding and depletion of effector cells all indicated that in vitro stimulation with HIV PR 76-84 or the IP-30 signal peptide activated a comparable population of cross-reactive effector cells. Neither IP-30 nor HIV PR 76-84 activated CTL against themselves following in vitro stimulation of PBMC from non-HIV-infected HLA-A2 individuals. Peptide titrations indicated higher-avidity T-cell interactions with HIV PR 76-84 than with the IP-30 signal peptide. These data indicate that HIV PR 76-84 is a heteroclitic variant of the IP-30 signal peptide -11 to -3, which has implications for immune memory and autoimmunity.     

A Literature Review of Blood-Disseminated P. marneffei Infection and a Case Study of this Infection in an HIV-Negative Child with Comorbid Eosinophilia

Mycopathologia - The typical manifestations of Penicillium marneffei (nowadays Talaromyces marneffei) infection in children without human immunodeficiency virus (HIV) remain unclear. The current...     

CD4-independent infection of two CD4(-)/CCR5(-)/CXCR4(+) pre-T-cell lines by human and simian immunodeficiency viruses

The infection of CD4-negative cells by variants of tissue culture-adapted human immunodeficiency virus type 1 (HIV-1) or HIV-2 strains has been shown to be mediated by the CXCR4 coreceptor. Here we show that two in vitro-established CD4(-)/CCR5(-)/CXCR4(+) human pre-T-cell lines (A3 and A5) can be productively infected by wild-type laboratory-adapted T-cell-tropic HIV-1 and HIV-2 strains in a CD4-independent, CXCR4-dependent fashion. Despite the absence of CCR5 expression, A3 and A5 cells were susceptible to infection by the simian immunodeficiency viruses SIVmac239 and SIVmac316. Thus, at least in A3 and A5 cells, one or more of the chemokine receptors can efficiently support the entry of HIV and SIV isolates in the absence of CD4. These findings suggest that to infect cells of different compartments, HIV and SIV could have evolved in vivo to bypass CD4 and to interact directly with an alternative receptor.     

Enhanced cellular immunity in macaques following a novel peptide immunotherapy

Advances in treating and preventing AIDS depend on understanding how human immunodeficiency virus (HIV) is eliminated in vivo and on the manipulation of effective immune responses to HIV. During the development of assays quantifying the elimination of fluorescent autologous cells coated with overlapping 15-mer simian immunodeficiency virus (SIV) or HIV-1 peptides, we made a remarkable observation: the reinfusion of macaque peripheral blood mononuclear cells, or even whole blood, pulsed with SIV and/or HIV peptides generated sharply enhanced SIV- and HIV-1-specific T-cell immunity. Strong, broad CD4+- and CD8+-T-cell responses could be enhanced simultaneously against peptide pools spanning 87% of all SIV- and HIV-1-expressed proteins-highly desirable characteristics of HIV-specific immunity. De novo hepatitis C virus-specific CD4+- and CD8+-T-cell responses were generated in macaques by the same method. This simple technique holds promise for the immunotherapy of HIV and other chronic viral infections.     

Human retroviral infections in The Gambia: prevalence and clinical features

The prevalence of infection with human immunodeficiency virus type 1 (HIV 1) is lower in west Africa than in other parts of Africa. Human immunodeficiency virus type 2 (HIV 2) has been isolated from west African patients and may be transmitted by heterosexual contact. The prevalence of antibodies to HIV 1 and HIV 2 was studied by enzyme linked immunosorbent assay (ELISA) among various groups of subjects in The Gambia, west Africa—namely, prostitutes, blood donors, patients with suspected infection with HIV, patients attending clinics for sexually transmitted diseases, and patients with tuberculosis. Four cases of the acquired immune deficiency syndrome (AIDS) due to infection with HIV 1 were detected, of which three had been acquired abroad. No other subject was found to be positive for antibodies to HIV 1. The prevalence of antibodies to HIV 2 among the patients attending clinics for sexually transmitted diseases was found to have increased from 0/117 in 1984 to 10/185 (5%) in the last six months of 1986. One out of 278 blood donors was positive for antibodies to HIV 2 as were 10 out of 80 patients with suspected AIDS.HIV 2 seems to be transmitted sexually, and, although it has been present for only a short time, it seems to be endemic in The Gambia and is pathogenic.