IBCN   20355
INSTITUTO DE BIOLOGIA CELULAR Y NEUROCIENCIA "PROFESOR EDUARDO DE ROBERTIS"
Unidad Ejecutora - UE
artículos
Título:
Increased Glial Fibrillary Acidic Protein Expression, Telomerase Activity and Telomere Length after Productive HIV-1 Infection of Cultured Murine Astrocytes
Autor/es:
OJEDA D.; LOPEZ JJ.; SEDE M.; LOPEZ EM.; BERRIA, MI; QUARLERI J.
Revista:
JOURNAL OF NEUROSCIENCE RESEARCH
Editorial:
WILEY-LISS, DIV JOHN WILEY & SONS INC
Referencias:
Lugar: New York; Año: 2014 vol. 92 p. 267 - 274
ISSN:
0360-4012
Resumen:
Although HIV-associated neurocognitive disorders
(HAND) result from injury and loss of neurons, productive
infection routinely takes place in cells of macrophage lineage.
In such a complex context, astrocytosis induced by
local chemokines/cytokines is one of the hallmarks of HIV
neuropathology. Whether this sustained astrocyte activation
is able to alter telomere-aging process is unknown.
We hypothesized that interaction of HIV with astrocytes
may impact astrocyte telomerase activity (TA) and telomere
length in a scenario of astrocytic activation measured
by expression of glial fibrillary acidic protein (GFAP).
To test this hypothesis, cultured murine astrocytes were
challenged with pseudotyped HIV/vesicular stomatitis
virus (HIV/VSV) to circumvent the absence of viral receptors;
and GFAP, telomerase activity, and telomere length
were quantified. As an early and transient event after HIV
infection, both TA activity and telomere length were significantly
augmented (P<0.001). Later, a strong negative
correlation (20.8616, P<0.0001) between virus production
and telomerase activity was demonstrated. Once HIV
production had reached a peak (7 dpi), the TA decreased,
showing levels similar to those of noninfected cells. In
contrast, the astrocyte became activated, exhibiting significantly
increased levels of GFAP expression directly
related to the level of HIV/VSV replication (P<0.0001).
Our results suggest that HIV-infected astrocytes exhibit
early disturbance in their cellular functions, such as telomerase
activity and telomere length, that may attenuate
cell proliferation and enhance the astrocyte dysregulation,
contributing to HIV neuropathogenesis. Understanding
the mechanisms involved in HIV-mediated persistence by
altering the telomere-related aging processes could aid in
the development of therapeutic modalities for neurological
complications of HIV infection.