HIV-1 biological phenotype in long-term infected individuals evaluated with an MT-2 cocultivation assay

Koot, M.; Vos, Annemieke; Keet, R.; Goede, R E de; Dercksen, Marli; Terpstra, Fokke G.; Coutinho, Roel A.; Miedema, Frank; Tersmette, M.

doi:10.1097/00002030-199201000-00006

Cited by 334 publications

(185 citation statements)

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“…Primary virus isolates were recovered from the PBMC of HIV ϩ partners of EU subjects (when available) and propagated in phytohemagglutinin-stimulated PBMC as described (19,25). All of these primary isolates were phenotyped by using the MT2 assay (26) and were determined to be nonsyncytium-inducing. One-ml aliquots of these ''mini'' bulk cultures were frozen at Ϫ70°C and the tissue culture infectious dose required to infect 50% of PBMCs (TCID 50 ) was determined for each virus isolate as described (27).…”

Section: Methodsmentioning

confidence: 99%

Lack of infection in HIV-exposed individuals is associated with a strong CD8⁺cell noncytotoxic anti-HIV response

Stranford

Skurnick

Louria

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

144

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Individuals repeatedly exposed to HIV, but who remain uninfected, form a population enriched for persons likely to have either natural or acquired resistance to the virus. We have studied four such exposed uninfected cohorts, representing 60 individuals, for evidence of protective immunity. This population included participants exposed to HIV through anal or vaginal receptive intercourse on multiple occasions over many years. We observed CD8؉ -cell noncytotoxic inhibition of HIV replication in acutely infected CD4 ؉ cells in the vast majority of individuals most recently exposed to the virus (within 1 year). The levels of this CD8 ؉ -cell response were sufficient to inhibit the in vitro infection of the exposed subjects' peripheral blood mononuclear cells. We found no evidence of a significant role for CCR5 ⌬32 mutation in this population, nor did CD4؉ cell susceptibility to infection or HIV-specific cytotoxic T-lymphocytes correlate with resistance to infection in the individuals tested. Therefore, the observed strong noncytotoxic CD8 ؉ -cell anti-HIV responses may be an antiviral immune activity contributing to the apparent protection from infection in these exposed uninfected individuals.

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Section: Methodsmentioning

confidence: 99%

Lack of infection in HIV-exposed individuals is associated with a strong CD8⁺cell noncytotoxic anti-HIV response

Stranford

Skurnick

Louria

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

144

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“…Following NSI to SI phenotype conversion however, the rate of CD4 cell depletion was on average 2 . 7-fold increased compared with the CD4 cell decline before SI development [17,19,20] (Fig. 1).…”

Section: Si Capacitymentioning

confidence: 96%

“…In progressive stages of HIV-1 infection the majority of virus variants present in infected individuals display increased replication rates, decreased capacity to replicate in macrophages but increased T-cell tropism [11][12][13][14][15] and in about 50% of infected individuals gain SI capacity [16,17]. This correlation between HIV-1 phenotype and the stage of infection suggests that HIV-1 phenotype variability plays an important role in the pathogenesis of AIDS.…”

Section: Introductionmentioning

confidence: 99%

Molecular determinants of human immunodeficiency virus type I phenotype variability

Fouchier

Schuitemaker

1996

Eur J Clin Investigation

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Abstract.The clinical course of HIV-1-infected individuals can be highly variable. Progression to AIDS can occur within 1 year after infection but symptom-free infection for more than 15 years has also been reported. This variation can either be determined by host factors, the biological variability of the virus or both. Here the molecular determinants and clinical relevance of HIV-1 biological phenotype variability are reviewed.

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“…The syncytiuminducing (SI) or non-Sl (NSI) phenotype of the viruses was determined in parallel with the antiviral assay by Antiviral Chemistry& Chemotherapy 8 (5) coculture of infected PBMCs with MT-2 cells. The cells were observed for the presence of syncytia, as described previously (Koot et al, 1992). (Felber & Pavlakis, 1988), in the presence or absence of different concentrations ofR-95288 at 3TC for 24 h. The cells were collected and lysed and the amount of CAT protein was measured by a commercial ELISA kit (Boehringer Mannheim).…”

Section: Antiviral Assaysmentioning

confidence: 99%

Anti-Human Immunodeficiency Virus Type 1 Activity of R-95288, a Phosphodiester Hexadeoxyribonucleotide Modified by Dibenzyloxybenzyl and Hydroxyethyl Residues at the 5′- and 3′-Ends

Agatsuma¹,

Furukawa²,

Hotoda

et al. 1997

Antivir Chem Chemother

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SummaryThe phosphodiester hexadeoxyribonucleotide R-95288 is a potent anti-human immunodeficiencr virus type 1 (HIV-1) agent in vitro which consists a a TGGGAG nucleoside sequence with dibenzyloxybenzyl and hydroxyethyl substituents at the 5'-and 3'-ends, respectively. In this study, the antiviral activity of R-95288 against various strains of HIV-1 in vitro was assessed and its mechanism of action was analysed. R-95288 inhibited replication of all strains of HIV-1 used including laboratory strains with the syncytium-inducing (51) phenotype and clinical isolates with both 51 and non-51 (NSI) phenotypes. The 50% inhibitory concentrations (lC 5 s) were 0.62-18~tg ml." (0.21-6.2~tM). R-95288 inhigited the binding and fusion of HIV-1-infected T cells with CD4+ cells. In addition, R-95288 specifically blocked the binding of monoclonal antibodies, recognizing the anti-V3 loop or the CD4-binding site of the virus envelope glycoprotein gp 120. Furthermore, the target site of R-95288 within the V3 loop was found in the putative heparin-binding region by binding inhibition assays using various anti-V3 loop antibodies. These results suggest that R-95288 can inhibit various strains of HIV-1, possibly by specific interaction with gp 120.

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HIV-1 biological phenotype in long-term infected individuals evaluated with an MT-2 cocultivation assay

Cited by 334 publications

References 0 publications

Lack of infection in HIV-exposed individuals is associated with a strong CD8⁺cell noncytotoxic anti-HIV response

Lack of infection in HIV-exposed individuals is associated with a strong CD8⁺cell noncytotoxic anti-HIV response

Molecular determinants of human immunodeficiency virus type I phenotype variability

Anti-Human Immunodeficiency Virus Type 1 Activity of R-95288, a Phosphodiester Hexadeoxyribonucleotide Modified by Dibenzyloxybenzyl and Hydroxyethyl Residues at the 5′- and 3′-Ends

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HIV-1 biological phenotype in long-term infected individuals evaluated with an MT-2 cocultivation assay

Cited by 334 publications

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Lack of infection in HIV-exposed individuals is associated with a strong CD8+cell noncytotoxic anti-HIV response

Lack of infection in HIV-exposed individuals is associated with a strong CD8+cell noncytotoxic anti-HIV response

Molecular determinants of human immunodeficiency virus type I phenotype variability

Anti-Human Immunodeficiency Virus Type 1 Activity of R-95288, a Phosphodiester Hexadeoxyribonucleotide Modified by Dibenzyloxybenzyl and Hydroxyethyl Residues at the 5′- and 3′-Ends

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Lack of infection in HIV-exposed individuals is associated with a strong CD8⁺cell noncytotoxic anti-HIV response

Lack of infection in HIV-exposed individuals is associated with a strong CD8⁺cell noncytotoxic anti-HIV response