Impaired replication of protease inhibitor-resistant HIV-1 in human thymus.
Nat Med
; 7(6): 712-8, 2001 Jun.
Article
em En
| MEDLINE
| ID: mdl-11385509
ABSTRACT
Many HIV-1-infected patients treated with protease inhibitors (PI) develop PI-resistant HIV-1 variants and rebounds in viremia, but their CD4+ T-cell counts often do not fall. We hypothesized that in these patients, T-cell counts remain elevated because PI-resistant virus spares intrathymic T-cell production. To test this, we studied recombinant HIV-1 clones containing wild-type or PI-resistant protease domains, as well as uncloned isolates from patients, in activated peripheral blood mononuclear cells, human thymic organ cultures and human thymus implants in SCID-hu Thy/Liv mice. In most cases, wild-type and PI-resistant HIV-1 isolates replicated to similar degrees in peripheral blood mononuclear cells. However, the replication of PI-resistant but not wild-type HIV-1 isolates was highly impaired in thymocytes. In addition, patients who had PI-resistant HIV-1 had abundant thymus tissue as assessed by computed tomography. We propose that the inability of PI-resistant HIV-1 to replicate efficiently in thymus contributes to the preservation of CD4+ T-cell counts in patients showing virologic rebound on PI therapy.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Timo
/
Replicação Viral
/
Linfócitos T
/
Infecções por HIV
/
Protease de HIV
/
HIV-1
/
Inibidores da Protease de HIV
Limite:
Adult
/
Animals
/
Humans
/
Middle aged
Idioma:
En
Revista:
Nat Med
Assunto da revista:
BIOLOGIA MOLECULAR
/
MEDICINA
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Estados Unidos