115 research outputs found
Kinetics of antiviral activity by human immunodeficiency virus type 1-specific cytotoxic T lymphocytes (CTL) and rapid selection of CTL escape virus in vitro
Kinetics of antiviral activity by human immunodeficiency virus type 1-specific cytotoxic T lymphocytes (CTL) and rapid selection of CTL escape virus in vitro
In vitro replication capacity of HIV-2 variants from long-term aviremic individuals
AbstractTo establish whether efficient suppression of virus replication in HIV-2-infected individuals is associated with low replicative capacity of HIV-2, replication kinetics of HIV-2 variants from long-term aviremic individuals was analyzed and compared with that of the relatively slow-replicating HIV-1 variants from asymptomatics and long-term nonprogressors (AS/LTNP). On average, HIV-2 from aviremic individuals had lower replication rates than HIV-1 variants from AS/LTNP in cells of 8 donors (0.45 log10 [range 0.14–0.77] vs. 0.58 log10 [range 0.32–0.99] pg RT/ml/day, P = 0.036). The relatively low replication rate of HIV-2 compared to HIV-1 variants was not related to different sensitivities to inhibition by CD8+ T cells or different degrees of infectivity. HIV-2 replication rates increased with progressive infection and with switch from CCR5 to CXCR4 usage.The relatively low replicative capacity of HIV-2 variants from aviremic individuals likely contributes to the low viral load and benign course of infection in these individuals
In vitro replication capacity of HIV-2 variants from long-term aviremic individuals
To establish whether efficient suppression of virus replication in HIV-2-infected individuals is associated with low replicative capacity of HIV-2, replication kinetics of HIV-2 variants from long-term aviremic individuals was analyzed and compared with that of the relatively slow-replicating HIV-1 variants from asymptomatics and long-term nonprogressors (AS/LTNP). On average, HIV-2 from aviremic individuals had lower replication rates than HIV-1 variants from AS/LTNP in cells of 8 donors (0.45 log10 [range 0.14-0.77] vs. 0.58 log10 [range 0.32-0.99] pg RT/ml/day, P = 0.036). The relatively low replication rate of HIV-2 compared to HIV-1 variants was not related to different sensitivities to inhibition by CD8+ T cells or different degrees of infectivity. HIV-2 replication rates increased with progressive infection and with switch from CCR5 to CXCR4 usage. The relatively low replicative capacity of HIV-2 variants from aviremic individuals likely contributes to the low viral load and benign course of infection in these individuals
Construction and characterisation of infectious recombinant HIV-1 clones containing CTL epitopes from structural proteins in Nef.
In this study the construction is described of HIV-1 molecular clones in which CTL epitopes from RT or Env late proteins were inserted into the Nef early protein. The ectopic epitopes were efficiently processed from the recombinant Nef proteins, were recognized by their cognate CTL in cytolytic assays, and did not perturb virus replication or viral protein expression in vitro. These recombinant viruses will therefore be an important tool in studying the effect of distinct epitope expression kinetics on the efficiency of CTL-mediated suppression of HIV-1 replication
Kinetics of antiviral activity by human immunodeficiency virus type 1-specific cytotoxic T lymphocytes (CTL) and rapid selection of CTL escape virus in vitro
The antiviral activity of a CD8(+) cytotoxic T-lymphocyte (CTL) clone
(TCC108) directed against a newly identified HLA-B14-restricted epitope,
human immunodeficiency virus type 1 (HIV-1) Rev(67-75) SAEPVPLQL, was
analyzed with respect to its kinetics of target cel
Coreceptor usage of human immunodeficiency virus type 2 primary isolates and biological clones is broad and does not correlate with their syncytium-inducing capacities
Entry of human immunodeficiency virus type 1 (HIV-1) into target cells is
mediated by binding of the surface envelope glycoprotein to the CD4
molecule. Interaction of the resulting CD4-glycoprotein complex with
alpha- or beta-chemokine receptors, depending on the biological phenotype
of the virus, then initiates the fusion process. Here, we show that
primary HIV-2 isolates and biological clones, in contrast to those of
HIV-1, may use a broad range of coreceptors, including CCR-1, CCR-3,
CCR-5, and CXCR-4. The syncytium-inducing capacity of these viruses did
not correlate with the ability to infect via CXCR-4 or any other
coreceptor. One cell-free passage of the intermediate isolates in
mitogen-stimulated, CD8+ cell-depleted peripheral blood mononuclear cells
resulted in the outgrowth of variants with CCR-5 only, whereas the
coreceptor usage of late and early isolates did not change. Since HIV-2 is
less pathogenic in vivo than HIV-1, these data suggest that HIV
pathogenicity in vivo is not directly related to the spectrum of
coreceptors used in in vitro systems
Broadening of coreceptor usage by human immunodeficiency virus type 2 does not correlate with increased pathogenicity in an in vivo model.
The pathogenic properties of four primary human immunodeficiency virus type 2 (HIV-2) isolates and two primary HIV-2 biological clones were studied in an in vivo human-to-mouse chimeric model. The cell-associated viral load and the ability to reduce the severity of the induced graft-versus-host disease symptoms, the CD4/CD8 ratio and the level of repopulation of the mouse tissues by the graft, were determined. All HIV-2 strains, irrespective of their in vitro biological phenotype, replicated to high titres and significantly reduced graft-versus-host disease symptoms as well as the CD4/CD8 ratios. Reduction of graft repopulation caused by infection with the respective HIV-2 strains showed that the in vitro replication rate, syncytium-inducing capacity and ability to infect human macrophages did influence the in vivo pathogenic potential whereas broadening of coreceptor usage did not
Decline of simian immunodeficiency virus (SIV)-specific cytotoxic T lymphocytes in the peripheral blood of long-term nonprogressing macaques infected with SIVmac32H-J5.
The evolution of simian immunodeficiency virus (SIV)–specific cytotoxic T lymphocyte precursors (CTLps) and their relationship with virus replication were studied in SIV‐infected macaques. After primary viremia, 3 of 8 macaques l
Validation of methods for converting the original Disease Activity Score (DAS) to the DAS28
© The Author(s) 2018.The Disease Activity Score (DAS) is integral in tailoring the clinical management of rheumatoid arthritis (RA) patients and is an important measure in clinical research. Different versions have been developed over the years to improve reliability and ease of use. Combining the original DAS and the newer DAS28 data in both contemporary and historical studies is important for both primary and secondary data analyses. As such, a methodologically robust means of converting the old DAS to the new DAS28 measure would be invaluable. Using data from The Early RA Study (ERAS), a sub-sample of patients with both DAS and DAS28 data were used to develop new regression imputation formulas using the total DAS score (univariate), and using the separate components of the DAS score (multivariate). DAS were transformed to DAS28 using an existing formula quoted in the literature, and the newly developed formulas. Bland and Altman plots were used to compare the transformed DAS with the recorded DAS28 to ascertain levels of agreement. The current transformation formula tended to overestimate the true DAS28 score, particularly at the higher end of the scale. A formula which uses all separate components of the DAS was found to estimate the scores with a higher level of precision. A new formula is proposed that can be used by other early RA cohorts to convert the original DAS to DAS28.Peer reviewedFinal Published versio
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