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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Baboons (Papio cynocephalus) provide a valuable animal model for the study of human immunodeficiency virus (HIV) pathogenesis because HIV-2 infection of baboons causes a chronic viral disease that progresses over several years before clinical signs of acquired immunodeficiency syndrome (AIDS) appear. Since HIV-2-infected baboons develop a chronic viral infection, insights into the immuno-biology of viral latency, clinical stages of disease, virus infection of lymphatic tissue and HIV transmission can be gained using this animal model. The development of an AIDS-like disease in baboons is viral isolate and baboon subspecies dependent. Thus, viral virulence factors and host resistance can be studied as well as the mechanisms of innate and acquired immunity. The control of virus infection is dependent upon cytotoxic and non-cytotoxic antiviral activity of CD8+ T cells. In this regard, some of the HIV-2-infected baboons develop potent antiviral cellular immune responses that have a similar magnitude to that found in HIV-1-infected long-term survivors (or non-progressors). In our laboratory, baboons have been used to study DNA vaccine strategies using new cationic liposome formulations and granulocyte macrophage-colony stimulating factor and B7-2 as genetic adjuvants. The results demonstrate the value of using baboons as an animal model of AIDS pathogenesis and vaccine development.
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PMID:Baboons as an animal model for human immunodeficiency virus pathogenesis and vaccine development. 1178 53

Primary human immunodeficiency virus type 2 (HIV-2) isolates are characterized by their ability to use a broad range of coreceptors, including CCR5, CXCR4, and several alternative coreceptors. However, the in vivo relevance of this in vitro promiscuity in coreceptor usage remains unclear. We set out to evaluate the relative importance of CCR5 and CXCR4 for infection of activated peripheral blood mononuclear cells (PBMC). PBMC from donors homozygous for wild-type CCR5 (CCR5(+/+) or CCR5Delta32 (CCR5(-/-)) were tested for their susceptibility to infection with 10 primary HIV-2 isolates with known coreceptor usage by parallel 50% tissue culture infectious dose (TCID50) titrations. Although all isolates, except one, were able to establish productive infection in CCR5(-/-) PBMC, the infection of these cells was inefficient for all isolates that were unable to use CXCR4. For CXCR4-using isolates there were only minor differences in TCID50 between CCR5(+/+) and CCR5(-/-) PBMC. When we compared the replication kinetics in PBMC from donors of the two genotypes we observed an average delay in replication onset of 9 days in the CCR5(-/-) PBMC. This study shows that HIV-2 can use alternative coreceptors for infection of PBMC, but that this infection is much less efficient than infection mediated by CCR5 or CXCR4. Thus, CCR5 and CXCR4 appear to be the major coreceptors for HIV-2 infection of PBMC.
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PMID:CCR5 or CXCR4 is required for efficient infection of peripheral blood mononuclear cells by promiscuous human immunodeficiency virus type 2 primary isolates. 1183 53

Similar to human immunodeficiency virus type 1 (HIV-1) infection of humans, the natural history of HIV-2 infection in baboons (Papio cynocephalus) is a slow and chronic disease that generally takes several years before an AIDS-like condition develops. To shorten the amount of time to the development of disease, we performed five serial passages of HIV-2(UC2) in baboons by using blood and bone marrow samples during the acute phase of infection when viral loads were at high levels. After these serial passages, virus levels in plasma, peripheral blood mononuclear cells (PBMC) and lymphatic tissues in the acutely infected baboons were increased. Within 1 year of the HIV-2 infection, all of the inoculated baboons showed specific signs of AIDS-related disease progression within the lymphatic tissues, such as vascular proliferation and lymphoid depletion. The HIV-2(UC2) recovered after four serial passages showed increased kinetics of viral replication in baboon PBMC and cytopathicity. This study suggests that the HIV-2 isolate recovered after several serial passages in baboons will be useful in future studies of AIDS pathogenesis and vaccine development by using this animal model.
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PMID:Increased virus replication and virulence after serial passage of human immunodeficiency virus type 2 in baboons. 1247 12

From a prospective cohort study of 1948 initially human immunodeficiency virus (HIV) uninfected female commercial sex workers followed between 1985 and 1999 in Dakar, Senegal, the authors compared the male to female per infectious sexual exposure transmission probability of HIV types one (HIV-1) and two (HIV-2). New non-parametric competing risks failure time methods were used, which minimized modelling assumptions and controlled for risk factors for HIV infection. The HIV-1 versus HIV-2 infectivity ratio over time was estimated by the ratio of smoothed non-parametric kernel estimates of the HIV-1 and HIV-2 infection hazard functions in sex workers, adjusted by an estimate of the relative HIV-1 versus HIV-2 prevalence in the partner population. HIV-1 was found to be significantly more infectious than HIV-2 throughout the follow-up period (P < 0.001). The HIV-1/HIV-2 infectivity ratio was inferred to be approximately constant over time, with estimated common value 3.55. The finding of greater HIV-1 infectivity persisted in sensitivity analyses and in covariate-adjusted analyses, with adjusted infectivity ratio estimates ranging between 3.40 and 3.86. Understanding the mechanisms by which HIV-1 infects more efficiently than HIV-2 may be useful in the development of HIV-1 vaccines. Additionally, the methodology developed here may be useful for analysing other data sets.
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PMID:Comparison of HIV-1 and HIV-2 infectivity from a prospective cohort study in Senegal. 1259 Apr 15

Fewer people infected with human immunodeficiency virus (HIV) type 2 progress to acquired immunodeficiency syndrome, compared with those infected with HIV-1. To understand the immune mechanisms leading to slow progression in HIV-2 infection, cell-mediated immune responses were compared between the 2 infections in asymptomatic subjects with a CD4 cell count > or =20%. Interferon- gamma release from T lymphocytes and the cytotoxicity of CD8+ T lymphocytes were measured by ELISPOT and 51Cr release assays. The level of responses and the proportion of responders were similar in the 2 infections, despite a 20-fold difference in their geometric mean plasma virus loads. The proliferation of CD4+ T helper cells, which was evaluated by thymidine incorporation, was not different between the 2 infections. Contrary to widely held views, our results suggest that nonprogression in HIV-2 infection may not be due to more vigorous immune responses.
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PMID:No differences in cellular immune responses between asymptomatic HIV type 1- and type 2-infected Gambian patients. 1474 8

Human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) are the causative agents of Acquired Immunodeficiency Syndrome (AIDS). Without therapeutic intervention, HIV-1 or HIV-2 infections in humans are characterized by a gradual and irreversible immunologic failure that ultimately leads to the onset of a severe immunodeficiency that constitutes the hallmark of AIDS. In the last two decades AIDS has evolved into a global epidemic affecting millions of persons worldwide. Although sharing several identical properties, HIV-1 and HIV-2 have shown some important differences in vivo. In fact, a significant amount of epidemiologic, clinical and virologic data suggest that HIV-2 is in general less virulent than HIV-1. This reduced virulence is revealed by the longer asymptomatic period and the smaller transmission rate that characteristically are observed in HIV-2 infection. In this context, studies using HIV-2 as a model of a naturally less pathogenic infection could bring important new insights to HIV pathogenesis opening to new strategies to vaccines or therapeutic design. The reasons underlying the reduced pathogenicity of HIV-2 are still essentially unknown and surely are the outcome of a combination of distinct factors. In this review we will discuss the importance and the possible implications in HIV-2 pathogenesis, particularly during the asymptomatic period, of a less fitted interaction between viral envelope glycoproteins and cellular receptors that have been described in the way HIV-2 and HIV-1 use these receptors.
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PMID:HIV-2 infection and chemokine receptors usage - clues to reduced virulence of HIV-2. 1563 19

We studied mortality among subjects with human immunodeficiency virus (HIV)-1 and HIV-2 infection in relation to GB virus (GBV)-C coinfection. No significant differences in mortality were seen between subjects with and subjects without GBV-C coinfection who also had either HIV-1 or HIV-2 infection. No association between GBV-C and HIV plasma virus loads or CD4 cell count was observed.
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PMID:No observed effect of GB virus C coinfection on disease progression in a cohort of African woman infected with HIV-1 or HIV-2. 1573 23

Clinical experience with the treatment of human immunodeficiency virus (HIV) type 2 (HIV-2) infection is limited, and even more scarce is information on therapy for patients coinfected with HIV type 1 (HIV-1) and HIV-2. Here, we describe the outcome for a coinfected patient in whom infection with both viruses was successfully controlled at the start of antiretroviral therapy, but for whom HIV-2 infection escaped control after a treatment simplification change while HIV-1 remained undetectable.
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PMID:Viral response to antiretroviral therapy in a patient coinfected with HIV type 1 and type 2. 1598 6

Pre-treatment serum levels of sCD163 were measured in a cohort of 236 suspected tuberculosis (TB) cases from Guinea-Bissau, with a median follow-up period of 3.3 years (range 0-6.4 years). In 113 cases, the diagnosis of TB was verified by positive sputum microscopy and/or culture. Among the verified TB cases, a decreased survival rate was found in 27 patients with sCD163 levels above the upper reference limit (3.95 microg/mL). The difference in survival was significant during TB treatment (log rank, p<0.02) and after long-term follow-up (log rank, p<0.001). The decrease in survival rate during TB treatment remained significant in a multivariate Cox model controlling for human immunodeficiency virus (HIV) status, age and gender, with a mortality increase of 1.19 (95% CI, 1.04-1.36) per microg of sCD163, and a hazard ratio (HR) for sCD163 levels above the upper reference limit of 4.18 (95% CI, 1.06-16.4). The difference was not significant after excluding patients with concomitant HIV-1 and HIV-2 infection in Kaplan-Meier analyses (log rank, p 0.11). In contrast, the difference in survival remained significant in Kaplan-Meier analyses after long-term follow-up, even after excluding patients with concomitant HIV-1 and HIV-2 infection (log rank, p 0.002). In the Cox model, the mortality increase per microg of sCD163 was 1.27 (95% CI, 1.14-1.40), with an HR for elevated sCD163 levels of 2.85 (95% CI, 1.44-5.63). The HRs for concomitant HIV-1 and HIV-2 infection were 6.92 (95% CI, 3.28-14.58) and 2.48 (95% CI, 1.09-5.67), respectively. Thus, sCD163 levels appeared to be an independent predictor of survival in verified TB patients.
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PMID:Predictive value of soluble haemoglobin scavenger receptor CD163 serum levels for survival in verified tuberculosis patients. 1610 88

To investigate why human immunodeficiency virus type 2 (HIV-2) is less virulent than HIV-1, the evolution of coreceptor usage, autologous neutralization, envelope sequence and glycosylation was studied in sequentially obtained virus isolates and sera from four HIV-2-infected individuals. Neutralization of primary HIV-2 isolates was tested by a cell line-based assay and IgG purified from patients' sera. Significant autologous neutralization was observed for the majority (39 of 54) of the HIV-2 serum-virus combinations tested, indicating that neutralization escape is rare in HIV-2 infection. Furthermore, sera from 18 HIV-2 patients displayed extensive heterologous cross-neutralization when tested against a panel of six primary HIV-2 isolates. This indicates that HIV-2 is intrinsically more sensitive to antibody neutralization than HIV-1. In line with earlier reports, HIV-2 isolates could use several alternative receptors in addition to the major coreceptors CCR5 and CXCR4. Intrapatient evolution from CCR5 use to CXCR4 use was documented for the first time. Furthermore, CXCR4 use was linked to the immunological status of the patients. Thus, all CXCR4-using isolates, except one, were obtained from patients with CD4 counts below 200 cells microl(-1). Sequence analysis revealed an association between coreceptor usage and charge of the V3 loop of the HIV-2 envelope, as well as an association between the rate of disease progression and the glycosylation pattern of the envelope protein. Furthermore, HIV-2 isolates had fewer glycosylation sites in the V3 domain than HIV-1 (two to three versus four to five). It is proposed here that HIV-2 has a more open and accessible V3 domain than HIV-1, due to differences in glycan packing, and that this may explain its broader coreceptor usage and greater sensitivity to neutralizing antibodies.
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PMID:Evolution of human immunodeficiency virus type 2 coreceptor usage, autologous neutralization, envelope sequence and glycosylation. 1629 86


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