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Originally published In Press as doi:10.1074/jbc.M110764200 on January 7, 2002
J. Biol. Chem., Vol. 277, Issue 12, 9825-9833, March 22, 2002
Syncytium Formation and HIV-1 Replication Are Both Accentuated by
Purified Influenza and Virus-associated Neuraminidase*
Jiangfeng
Sun ,
Benoit
Barbeau§,
Sachiko
Sato§,
Guy
Boivin¶,
Nathalie
Goyette, and
Michel J.
Tremblay
From the Centre de Recherche en Infectiologie, Hôpital du
Centre Hospitalier Universitaire de L'Université Laval,
Centre Hospitalier Universitaire de Québec, and Département
de Biologie médicale, Faculté de Médecine,
Université Laval, Ste-Foy,
Québec G1V 4G2, Canada
The degree of sialylation has been shown
previously to modulate the process of human immunodeficiency virus
type-1 (HIV-1) infection by affecting the interaction between the virus
and CD4-expressing target cells. In the present study, we investigated
whether HIV-1 replication cycle was affected by neuraminidase (NA)
derived from the human influenza (flu) virus. We first
demonstrate that the level of HIV-1-mediated syncytium formation was
greatly enhanced in the presence of purified flu NA. Pretreatment of
established monocytic and lymphocytic cell lines as well as primary
mononuclear cells with purified flu NA augmented also the process of
virus infection. A comparable up-regulating effect was observed when using several strains of UV-inactivated whole flu virus, thereby suggesting that virus-anchored NA enzymes positively modulate the HIV-1
life cycle. Furthermore, flu NA-mediated positive effect on HIV-1
biology was abrogated with zanamivir, a specific flu NA
inhibitor. Our results provide a new model allowing the
investigation of the potential benefit of using NA inhibitors in the
treatment of HIV-1-infected patients suffering from coinfection with
NA-bearing pathogens.
*
This work was supported in part by a grant from the Canadian
Foundation for AIDS Research (to B. B., S. S., and M. J. T.) and by Grants HOP-14438, MOP-37781, and HOP-15575 from the
Canadian Institute of Health Research HIV/AIDS Research Program (to
M. J. T.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
This work was performed in partial fulfillment of the requirements
for a M.Sc. degree in the Microbiology-Immunology Program at Laval University.
§
Recipient of scholarship awards (Junior 1 level) from the Fonds de
la Recherche en Santé du Québec (FRSQ).
¶
Recipient of scholarship awards (Junior 2 level) from the FRSQ.
Holder of a Senior Canada Research Chair in Human
Immuno-Retrovirology. To whom correspondence should be addressed:
Laboratoire d'Immuno-Rétrovirologie Humaine, Center de Recherche
en Infectiologie, RC709, Hôpital CHUL (CHUQ), 2705 boul. Laurier,
Ste-Foy, Québec G1V 4G2, Canada. Tel.: 418-654-2705; Fax:
418-654-2212; E-mail: michel.j.tremblay@crchul.ulaval.ca.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.
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