HIV-1 infection downregulates nuclear telomerase activity on lymphoblastoic cells without affecting the enzymatic components at the transcriptional level.
Both increased lymphocyte renewal with subsequent exhaustion of the immune system and impaired T cell renewal have been put into view to account for CD4+ T cell depletion and development of AIDS in HIV-1- infected humans. Telomerase is an enzyme that is involved in mechanisms that control cell life span and replicative potential. The effect of HIV-1 on telomerase activity, certain regulators, and telomeric terminal restriction fragment length on lymphoid Jurkat cells was used in measuring the proliferative activity of T lymphoid cells before and after being infected. At the cellular level, the enzymatic activity remains almost stable but further analyses of fractionated cells revealed that telomerase activity in the nuclear compartment was diminished whereas in the cytoplasmic compartment it was relatively increased on HIV-1 infection. Two key components of telomerase regulation were further considered at the transcriptional level, that is, the mRNA levels of both human telomerase reverse transcriptase (hTERT)--including the relative amount of its alternative splicing variants--and hTR. They were unaffected on HIV-1 infection. Telomeric length was also conserved in infected cells. Overall, these findings demonstrate that HIV-1 infection of Jurkat cells down modulate telomerase activity in the nuclear compartment by affecting its cellular localization.
Reynoso
R
R
Centro Nacional de Referencia para el SIDA, Departamento de Microbiología Facultad de Medicina, Universidad de Buenos Aires, 1121 Buenos Aires, Argentina.
Minces
L
L
Salomon
H
H
Quarleri
J
J
D002467:Cell Nucleus / Q000201:enzymology*; D015536:Down-Regulation; D015658:HIV Infections / Q000201:enzymology* / Q000821:virology*; D015497:HIV-1; D006801:Humans; D019169:Jurkat Cells; D013601:T-Lymphocytes / Q000378:metabolism*; D019098:Telomerase / Q000378:metabolism*; D014158:Transcription, Genetic
D019098:Telomerase