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Viral Phenotype (viral + phenotype)
Selected AbstractsMolecular characterization of the env gene of two CCR5/CXCR4-independent human immunodeficiency 2 primary isolates,JOURNAL OF MEDICAL VIROLOGY, Issue 11 2009Quirina Santos-Costa Abstract Human immunodeficiency virus 2 (HIV-2) infection is characterized by a slower disease progression and lower transmission rates. The molecular features that could be assigned as directly involved in this in vivo phenotype remain essentially unknown, and the importance of HIV-2 as a model to understand pathogenicity of HIV infection has been frequently underestimated. The early events of the HIV replication cycle involve the interaction between viral envelope glycoproteins and cellular receptors: the CD4 molecule and a chemokine receptor, usually CCR5 or CXCR4. Despite the importance of these two chemokine receptors in human immunodeficiency virus 1 (HIV-1) entry into cells, we have previously shown that in some HIV-2 asymptomatic individuals, a viral population exists that is unable to use both CCR5 and CXCR4. The goal of the present study was to investigate whether possible regions in the env gene of these viruses might account for this phenotype. From the molecular characterization of these env genes we could not detect any correlation between V3 loop sequence and viral phenotype. In contrast, it reveals the existence of remarkable differences in the V1/V2 and C5 regions of the surface glycoprotein, including the loss of a putative glycosilation site. Moreover, in the transmembrane glycoprotein some unique sequence signatures could be detected in the central ectodomain and second heptad repeat (HR2). Some of the mutations affect well-conserved residues, and may affect the conformation and/or the dynamics of envelope glycoproteins complex, including the SU,TM association and the modulation of viral entry function. J. Med. Virol. 81:1869,1881, 2009. © 2009 Wiley-Liss, Inc. [source] Isolation and biological characterization of HIV-1 BG intersubtype recombinants and other genetic forms circulating in Galicia, SpainJOURNAL OF MEDICAL VIROLOGY, Issue 12 2006Lucía Pérez-Alvarez Abstract The biological characteristics of HIV-1 primary isolates of different recombinant forms (RFs) and non-B subtypes from Galicia, Spain, were investigated and the relationships between biological phenotype and evolution of infection were determined. Peripheral blood mononuclear cells (PBMCs) were obtained during the follow-up of 32 patients infected with HIV-1 non-subtype B genetic forms, characterized in partial sequences of pol (protease-reverse transcriptase) and env V3 region: 12 (37.5%) circulating RFs (CRFs), 9 (28.1%) unique RFs (URFs), and 11(34.4%) non-B subtypes. Primary isolates were obtained by coculture with donor PBMCs. Syncytium-inducing (SI) phenotype was examined in MT2 cell line and coreceptor use in GHOST and U87.CD4 cells. Fifty percent of tissue culture infective dose (TCID50) and viral phenotype based on V3 net charge and Geno2phenocoreceptor bioinformatic method were determined. Fifty-four HIV-1 primary isolates were obtained. CRF14_BG and BG URFs represented the largest group, being all SI/X4, independently of the CD4+ cell count, viral load, or the duration of infection. By contrast, 10 of 11 CRF02_AG viruses were NSI/R5. The prediction of co-receptor use was concordant with biological characterization in all NSI/R5 and in 23 of 26 SI/X4 isolates. The presence of SI/X4 or SI/X4,R5 isolates at early stages of the infection in addition to a decrease in CD4+ counts below 500 cells/µl between 2 and 6 years since diagnosis was observed in all patients infected with CRF14_BG and BG URFs. These data contrast with the usual progression in B subtype infections, in which SI/X4 viruses rarely predominate in the early years of HIV-1 infection. J. Med. Virol. 78:1520,1528, 2006. © 2006 Wiley-Liss, Inc. [source] High specificity of V3 serotyping among human immunodeficiency virus type-1 subtype C infected patients with varying disease status and viral phenotypeJOURNAL OF MEDICAL VIROLOGY, Issue 10 2006Polly R. Walker Abstract V3 serotyping is a technique for determining HIV-1 genetic subtype based on the binding of antibodies from patient sera or plasma to synthetic V3 peptides derived from subtype consensus sequences. Variation in the performance of this assay has been attributed to V3 sequence heterogeneity, the degree of which varies with patient disease progression, virus co-receptor usage, and genetic subtype. This study assessed the performance of a competitive peptide enzyme immunoassay (cPEIA) in samples from HIV-1 subtype C infected patients with varying disease profiles, including those with syncytium (SI) and non-syncytium-inducing (NSI) viruses. Out of 90 sera tested, 94.4% reacted strongly against the subtype C peptide. There was no significant difference in assay sensitivity among samples from advanced AIDS patients in which humoral immune response may be lower, nor among SI viruses which carry changes in the V3 sequence. Four samples were found to be cross-reactive with other subtypes and one acutely infected patient sample was non-reactive due to low anti-gp120 antibody titers. A significantly higher number of samples showed secondary reactivity to subtype A, compared to other subtypes (P,<,0.005). In conclusion, the assay was able to identify HIV-1 subtype C infection with a high level of sensitivity (94%) irrespective of the stage of disease and therefore provides a valuable resource for the large-scale epidemiological monitoring of the spread of HIV-1 subtypes in South Africa. J. Med. Virol. 78:1262,1268, 2006. © 2006 Wiley-Liss, Inc. [source] Role of antiretroviral therapies in mucocutaneous manifestations in HIV-infected children over a period of two decadesBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2005E. Seoane Reula Summary Background, Human immunodeficiency virus (HIV) infection causes a severe cellular immunodeficiency, which results in a greater susceptibility to infectious, inflammatory and malignant conditions. Among these, pathologies of the skin seem to be those most frequently observed in HIV+ patients. However, there are few reports on how antiretroviral therapy affects skin disorders in HIV-infected children. Objective, To study the incidence and prevalence of skin disorders in a cohort of HIV-infected children, in relation to the antiviral therapy [nontreated, monotherapy, combined therapy and highly active antiretroviral therapy (HAART)] received, and their impact on immunological and virological markers. The treatments were those available in different calendar periods in the history of antiviral treatment. Materials and methods, A retrospective, observational study in a cohort of 210 HIV-infected children was carried out. These children were followed up every 3 months throughout 22 years. The viral load (HIV RNA copies mL,1) was quantified using reverse transcriptase-polymerase chain reaction and the viral phenotype of HIV-1 isolates was determined by in vitro culture. T-lymphocyte subsets in peripheral blood were quantified by flow cytometry. Results, Mucocutaneous manifestations were diagnosed in 17% of the untreated infected children. Of the treated children in different treatment periods, 22% in the monotherapy period, 25% in the combined therapy period but only 10% on HAART had some type of mucocutaneous manifestation, concordant with a higher number of CD4+ T cells, a lower viral load and less cytopathic virus in the last group. Mucocutaneous manifestations of infectious aetiology were most frequently observed; they were detected in 13% of the children during the first calendar period (untreated children), 16% during the second and third periods (monotherapy and combined therapy) and only 5% in the last period (HAART). Interestingly, syncytium-inducing virus was present in 69% of all children with mucocutaneous manifestations of infectious aetiology. Conclusion, Only in the last calendar period (HAART) was a significant decrease observed in the prevalence of mucocutaneous manifestations with HIV infection associated with an increase in CD4+ T cells. In addition, we found a strong association between children who had mucocutaneous manifestations with an infectious aetiology and a more cytopathic (X4/SI) viral phenotype. [source] Homeostatic role of IL-7 in HIV-1 infected children on HAART: Association with immunological and virological parametersACTA PAEDIATRICA, Issue 2 2005S Resino Abstract Aim: To investigate the role of IL-7 in HIV-infected children on highly active antiretroviral therapy (HAART) and its association with laboratory parameters related to disease progression. Patients and methods: A cross-sectional study in 31 vertically HIV-infected children (median age 8.4 y) treated with HAART, and a longitudinal study in four of those same children was carried out. In both studies, viral load, CD4+ T-cell counts, thymic production of T cells by TCR rearrangement excision circles (TRECs), IL-7 plasma levels and viral phenotype were determined. Results: IL-7 levels were higher in HIV-infected children than in age-matched, uninfected controls. In addition, HIV children with CD4+ T cells between 200 and 500 T cells/mm3 had higher IL-7 levels and lower TREC values than HIV-infected children with CD4+ T cells >500 T cells/mm3. IL-7 levels were higher in children with syncytium-inducing (SI) phenotype than in those with non-syncytium-inducing (NSI) variants. During the follow-up of four HIV children, the decrease in viral load after HAART was always associated with a recovery of CD4+ T cells and TRECs, which was followed by a decrease in IL-7 returning to the levels present prior to the drop in CD4+ T cells. The four HIV-infected children had SI/X4 isolates in PBMC before HAART, and the viral phenotype switched to NSI/R5 after HAART. Conclusion: Our data suggest that IL-7 plays a key role in the maintenance of T-cell homeostasis in HIV-infected children on HAART, both through peripheral expansion and through a thymus-dependent mechanism. [source] Mother-to-infant transmission of SIV via breast-feeding in rhesus macaquesJOURNAL OF MEDICAL PRIMATOLOGY, Issue 4-5 2003A.M. Amedee Abstract: 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. [source] |