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Journal of Virology, May 2000, p. 4634-4644, Vol. 74, No. 10
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Influenza Virus Assembly and Lipid Raft
Microdomains: a Role for the Cytoplasmic Tails of the Spike
Glycoproteins
Jie
Zhang,1
Andrew
Pekosz,2 and
Robert A.
Lamb1,2,*
Department of Biochemistry, Molecular Biology
and Cell Biology1 and Howard Hughes
Medical Institute,2 Northwestern University,
Evanston, Illinois 60208-3500
Received 5 January 2000/Accepted 16 February 2000
Influenza viruses encoding hemagglutinin (HA) and neuraminidase
(NA) glycoproteins with deletions in one or both cytoplasmic tails
(HAt
or NAt
) have a reduced association with detergent-insoluble glycolipids (DIGs). Mutations which eliminated various combinations of
the three palmitoylation sites in HA exhibited reduced amounts of
DIG-associated HA in virus-infected cells. The influenza virus matrix
(M1) protein was also found to be associated with DIGs, but
this association was decreased in cells infected with HAt
or NAt
virus. Regardless of the amount of DIG-associated protein, the HA and
NA glycoproteins were targeted primarily to the apical surface of
virus-infected, polarized cells. The uncoupling of DIG association and
apical transport was augmented by the observation that the influenza A
virus M2 protein as well as the influenza C virus
HA-esterase-fusion glycoprotein were not associated with DIGs but were
apically targeted. The reduced DIG association of HAt
and NAt
is an
intrinsic property of the glycoproteins, as similar reductions in DIG
association were observed when the proteins were expressed from cDNA.
Examination of purified virions indicated reduced amounts of
DIG-associated lipids in the envelope of HAt
and NAt
viruses. The
data indicate that deletion of both the HA and NA cytoplasmic tails
results in reduced DIG association and changes in both virus
polypeptide and lipid composition.
*
Corresponding author. Mailing address: Department of
Biochemistry, Molecular Biology and Cell Biology, Northwestern
University, 2153 North Campus Dr., Evanston, IL 60208-3500. Phone:
(847) 491-5433. Fax: (847) 491-2467. E-mail:
ralamb{at}northwestern.edu.
Journal of Virology, May 2000, p. 4634-4644, Vol. 74, No. 10
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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