TY - JOUR
T1 - HIV-1 infection of the thymus
T2 - Evidence for a cytopathic and thymotropic viral variant in vivo
AU - Calabro, M. L.
AU - Zanotto, C.
AU - Calderazzo, F.
AU - Crivellaro, C.
AU - Del Mistro, A.
AU - De Rossi, A.
AU - Chieco-Bianchi, L.
PY - 1995
Y1 - 1995
N2 - As thymocyte infection may represent one of the mechanisms responsible for CD4+ T lymphocyte depletion in HIV-1-infected individuals, we studied the occurrence of HIV-1 infection in the thymus in vivo. Thymus (THY(PD)) and peripheral blood (PBL(PD)) primary viral isolates were obtained from an HIV- 1-infected patient; restriction pattern analysis revealed the presence of a viral variant (THY) in the thymus isolate, from which biological viral clones containing this variant were obtained by limiting dilution infection of Molt- 3 cells. The biological phenotype of the viral isolates and THY clones was studied in different cell lines and primary cultures. PBL(PD), THY(PD), and THY clones could efficiently infect T cell lines; the thymic variant showed a higher cytopathic activity in T cell lines, and a higher replication capacity in both unfractionated and CD4+CD8+enriched primary thymocytes. Sequence analysis of the viral population patterns in vivo confirmed the presence of the THY variant in the thymic compartment, and revealed that the degree of V3 loop heterogeneity was higher in the thymocytes of the patient than in the peripheral blood lymphocytes. In addition to confirming thymocyte infection in vivo, our data also indicate that a differential distribution of viral variants may occur among different body compartments in a single individual; the emergence of cytopathic and tissue-specific variants in the thymus may play a relevant role in the pathogenesis of HIV-1 disease.
AB - As thymocyte infection may represent one of the mechanisms responsible for CD4+ T lymphocyte depletion in HIV-1-infected individuals, we studied the occurrence of HIV-1 infection in the thymus in vivo. Thymus (THY(PD)) and peripheral blood (PBL(PD)) primary viral isolates were obtained from an HIV- 1-infected patient; restriction pattern analysis revealed the presence of a viral variant (THY) in the thymus isolate, from which biological viral clones containing this variant were obtained by limiting dilution infection of Molt- 3 cells. The biological phenotype of the viral isolates and THY clones was studied in different cell lines and primary cultures. PBL(PD), THY(PD), and THY clones could efficiently infect T cell lines; the thymic variant showed a higher cytopathic activity in T cell lines, and a higher replication capacity in both unfractionated and CD4+CD8+enriched primary thymocytes. Sequence analysis of the viral population patterns in vivo confirmed the presence of the THY variant in the thymic compartment, and revealed that the degree of V3 loop heterogeneity was higher in the thymocytes of the patient than in the peripheral blood lymphocytes. In addition to confirming thymocyte infection in vivo, our data also indicate that a differential distribution of viral variants may occur among different body compartments in a single individual; the emergence of cytopathic and tissue-specific variants in the thymus may play a relevant role in the pathogenesis of HIV-1 disease.
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M3 - Article
C2 - 7734184
AN - SCOPUS:0029004746
VL - 11
SP - 11
EP - 19
JO - AIDS Research and Human Retroviruses
JF - AIDS Research and Human Retroviruses
SN - 0889-2229
IS - 1
ER -