摘要:

Summary:HIV‐1 appears to use a multiple gene strategy to regulate CD4 receptor expression, which emphasizes the importance of this regulation in the viral life cycle. The cytoplasmic interaction between gp160 and CD4 is probably the major event governing CD4 down‐regulation, although other viral proteins, such as Nef (CD4 cell surface localization) and Vpu (CD4 degradation), are thought to participate as well. Because of the lack of vpu in HIV‐2, we investigated the effects of two HIV‐2 isolates (ROD 10 and EHO) on CD4 expression in the CEM T‐cell line. We found that these HIV‐2 strains induce CD4 degradation to a similar extent as that induced by an HIV‐1 isolate (BRU). To assess the role of each viral protein involved in CD4 regulation (gp, Nef and Vpu), we developed cell lines expressing a mutated form of CD4 unable to efficiently bind gp160, in addition to their endogenous CD4. Using this system, we provide evidence that the mutated CD4 is always expressed in HIV‐1‐, and HIV‐2‐infected cells, independent of the presence of Nef, while the endogenous CD4 is completely lost. These results highlight the key role of intracytoplasmic gp‐CD4 interaction, explaining in vitro the CD4 down‐regulation in T‐cell lines.

ISSN:1077-9450    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Summary:We examined the ability of human immunodeficiency virus (HIV) type 1 (HIV‐1) to infect in vitro, primary brain‐derived human microvascular endothelial cells (HMEC) that constitute the blood‐brain barrier (BBB). Immunofluorescence (IFA) and antigen capture assays failed to demonstrate p24 antigen from HIV inoculated endothelial cells and supernatants did not contain detectable levels of reverse transcriptase (RT). HIV could be rescued by cocultivation of infected HMEC with a susceptible T‐lymphocyte line (CEM‐SS), which were then shown to form syncytia and produce RT activity and p24 Ag (IFA, antigen captive assay). Polymerase chain reaction (PCR) was successfully used to amplify HIV‐specificgagandenvgene sequences from HMEC. CD4 expression was not identified on these cells by IFA. These results suggest that HIV infection of BBB endothelium occurs, but that viral replication is minimal. Infection of the BBB by HIV may give the virus a foothold in the CNS and suggests that the brain might be infected directly and may not be limited to just the passage of infected mononuclear cells.

ISSN:1077-9450    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Summary:The level of human immunodeficiency virus type 1 (HIV‐1) RNA in human plasma has been quantitated directly with use of a solid‐phase nucleic acid hybridization assay, based on branched DNA (bDNA) signal amplification technology with chemiluminescent detection. Signal amplification is accomplished by the incorporation of sites for 1,755 alkaline phosphatase‐labeled probes per genome of HIV‐1, after successive hybridization of target‐specific oligonucleotides and bDNA amplifier molecules. The assay is performed in microwells, much like an immunoassay, and is amenable to routine laboratory use. Reproducibility and specificity studies indicated that the bDNA method was precise and showed no reactivity with seronegative donors. HIV‐1 RNA levels were quantitated for 348 seropositive specimens, with a detection rate of 83% for those specimens from patients with <500 CD4+T‐cell counts. Plasma RNA levels were found to change with disease stage, and in response to antiviral therapy. Quantitation of HIV‐1 RNA in the plasma of HIV‐1‐infected patients, with use of the bDNA assay, may be a useful method for monitoring HIV‐1 disease progression and therapeutic response.

ISSN:1077-9450    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Summary:Kaposi's sarcoma (KS) is the most common tumor seen in patients with HIV‐1 infection. HIV‐1 may induce KS directly through viral protein(s) or indirectly through regulation of cytokines such as IL‐1 and IL‐6. We have shown that AIDS‐KS spindle cells express IL‐1&bgr; and that IL‐1ra inhibits KS‐spindle cell growth. IL‐1ra had little effect on human umbilical vein endothelial cells (HUVEC), human aortic smooth muscle cells (HASM), and human foreskin fibroblast (NN41). These findings support an autocrine activity for IL‐1. Furthermore, exogenous IL‐1 can enhance AIDS‐KS cell growth, and this effect is completely blocked by IL‐1ra. As expected, IL‐1ra also blocks IL‐1 mediated upregulation of IL‐6 and bFGF, both of which are autocrine growth factors for KS. IL‐1ra is thus a potential candidate for the treatment of AIDS‐associated KS.

ISSN:1077-9450    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Summary:Persons infected with human immunodeficiency virus (HIV) are at greater risk of infection withListeria monocytogenes(LM) than the general population. We quantify the risk of listeriosis in persons with acquired immune deficiency syndrome (AIDS) and HIV infection in Los Angeles County (LAC) and report the LM serotype distribution among HIV‐infected patients with listeriosis. Active surveillance for listeriosis was performed in LAC during most of the period from 1985 through 1992. Thirty‐four (10%) of 351 nonperinatal cases of listeriosis reported in LAC from 1985 through 1992 were in HIV‐infected persons, 25 of whom met the 1987 AIDS case definition. The incidence of listeriosis was 95.8 and 8.8 cases per 100,000 person‐years among persons with AIDS and all HIV‐infected persons, respectively, but only 1.0 case per 100,000 person‐years in the total population. Excluding cases from a 1985 listeriosis epidemic associated with consumption of contaminated Mexican‐style cheese, 11 (65%) of 17 HIV‐infected persons with available isolates were infected with LM serotype 1/2b, whereas only 64 (31%) of 208 other persons with listeriosis and available isolates were infected with LM serotype 1/2b (odds ratio = 4.1; 95% confidence interval = 1.3‐14.1). LM serogroup 1/2b may have been more common among HIV‐infected persons in LAC than among other persons with listeriosis because of differences in diet or sexual practices, or to chance alone. Persons with HIV‐infection, especially those with AIDS, should be educated in avoiding foods at high risk of listerial contamination, such as soft cheeses, food sold from delicatessen counters, and undercooked chicken.

ISSN:1077-9450    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Summary:A total of 113 patients with infection due to human T‐cell leukemia virus type 1 (HTLV‐I) were evaluated at the University of Miami from January 1988 to March 1993. Forty patients were identified with adult T‐cell leukemia/lymphoma (ATLL) and 63 with HTLV‐I‐associated myelopathy (HAM). Three had concomitant ATLL and HAM. Two HAM patients co‐infected with human immunodeficiency virus type 1 (HIV‐I) developed clonal lymphopro‐ liferative disease during the study period. Patients with ATLL have a poor prognosis; multiple chemotherapy regimens including high‐dose cytotoxic agents have been utilized with a small impact on survival. Most of our patients are currently treated with experimental regimens. Rheumatologic or autoimmune illnesses were identified, mostly in HAM patients, and a small number developed immunodeficiencies in the absence of other definable etiologic factors. Most of the patients were immigrants from areas of endemicity in the Caribbean basin, although many Americans were also recognized. HTLV‐I/II infection was diagnosed serologically and typed as HTLV‐I by polymerase chain reaction (PCR) or a modified Western blot when a DNA sample was not available. In 24 of 40 patients with ATLL, Southern blot hybridization performed on DNA extracted from peripheral blood lymphocytes or tumor tissue demonstrated clonal HTLV‐I integration. In South Florida, ATLL and HAM are now seen frequently. Since HTLV‐I infection is associated with a 4% lifetime risk of developing ATLL and an additional 0.25% lifetime risk for developing HAM, a large pool of asymptomatically infected individuals must exist here. Autoimmune conditions and immunodeficiency states are not uncommon in these patients. Unusual clinical presentations are now being recognized in those co‐infected with HTLV‐I and HIV‐I.

ISSN:1077-9450    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Summary:Seroconverting men in the Vancouver Lymphadenopathy—Acquired Immune Deficiency Syndrome Study cohort were studied in this analysis to estimate the waiting times in the different stages of the modified World Health Organization (WHO) staging system for human immunodeficiency virus infection. A time‐homogeneous staged Markov model was used, and it was assumed that infected individuals progress irreversibly from Stages I to IV and eventually to death. There were 130 individuals who seroconverted during the study (seroincident) and were included in this analysis. With use of the modified WHO staging system, the estimated mean waiting times for progression to Stage IV were 9.5, 6.5, and 2.0 years from stages I, II, and III, respectively. The estimated survival times were 11.2, 8.2, 3.7, and 1.7 years from Stages I to IV, respectively. Waiting times and survival were not significantly different when the lymphocyte count was used instead of the CD4 cell count in application of the staging system. The application of a staged Markov model to the modified WHO staging system suggests that this is a clinically sensible model. Furthermore, our results confirm that in the absence of CD4 cell counts, lymphocyte counts can be used as an alternative without substantial loss of information.

ISSN:1077-9450    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Summary:Previous reports from our laboratory have shown that complement activation and the presence of circulating immune complexes are features of congenital human immunodeficiency virus (HIV) infection as they are in HIV‐ infected adults. The studies reported here were undertaken to (a) define whether complement activation is congenitally infected infants and children involves classic, alternative, or both pathways; (b) investigate the relationship between complement activation and circulating immune complexes; and (c) determine how early in congenital HIV infection complement activation and immune complexes can be found. We report that classic complement pathway activation and C1q‐binding immune complexes can be found within the first 4 months of congenital HIV infection. However, the association between classic pathway activation and immune complexes before age 10 months was weak. These data raise interesting questions about complement‐mediated immune complex processing in HIV‐infected infants and young children.

ISSN:1077-9450    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Summary:To further characterize the natural history of HIV infection in women in the antiretroviral era, we performed a longitudinal, descriptive analysis of demographic features, clinical characteristics, patterns of antiretroviral and prophylactic therapy, disease progression, and survival in a cohort of women followed at a university medical center from 1986 to 1992. Eighty‐two women (39 white [non‐Hispanic], 33 African‐American, 10 Hispanic) were followed for a median of 13 months (range 3‐61 months). Sixty‐two women received antiretroviral therapy, 34 through participation in a clinical trial.Candidaesophagitis andPneumocystis cariniipneumonia were the most common AIDS‐defining conditions, accounting for 77% of all initial AIDS‐defining diagnoses. Gynecologic complications affected 34 women (41%) and included recurrentCandidavaginitis in 26, abnormal PAP smears/cervical intraepithelial neoplasia in 10, and recurrent genital herpes simplex virus disease in seven. Median survival (Kaplan‐Meier) from the time of HIV serodiagnosis was >59 months; median survival following an AIDS diagnosis was 27 months. No survival differences were detected based on race, insurance status, or mode of HIV transmission. Women who participated in antiretroviral therapy clinical trials had a statistically significantly longer duration of survival compared with nonparticipants.Candidainfections and gynecologic diseases were common in this population. Overall survival was similar to that reported for men.

ISSN:1077-9450    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Summary:To characterize long‐term survival with HIV‐1, we need to estimate the proportion of seroconverters remaining free from clinical AIDS for long periods. We predict that ˜13% of homosexual/bisexual men infected at a young age may remain so for >20 years. Since studies have not followed individuals for such periods, long‐term survivors must be characterized using stability of immunologic markers. In a cohort of 1,809 seropositive men followed since 1984‐85, 15% (187/1,214) of those with at least two consecutive visits early in the study showed no decline in CD4+cell count. From these, 67 men with long follow‐up and no use of zidovudine were identified as cases to investigate correlates of protection against HIV‐1‐induced immunodepletion. Two matched control subgroups, one with moderate and one with rapid CD4+lymphocyte decline, produced 56 triplets of individuals to be contrasted. Analysis of data from early in the study on demographics, sexual behavior, and sexually transmitted diseases revealed no significant differences among the three groups. Men showing no decline in CD4+lymphocytes persistently showed a healthier profile with respect to onset of clinical AIDS, survival, and concomitant hematologic variables. Moderate decliners had rates of clinical AIDS and death significantly higher than those in the stable group but lower than the fast decliners.

ISSN:1077-9450    

出版商:OVID    

年代:1995

数据来源: OVID