Carbohydrates comprise about 50% of the mass of gp120, the external envelope glycoprotein of simian immunodeficiency virus (SIV) and human immunodeficiency virus We identified 11 replication-competent derivatives of SIVmac239 lacking two, three, four, or five potential sites for N-linked glycosylation These sites were located within and around variable regions 1 and 2 of the surface envelope protein of the virus Asn (AAT) of the canonical N-linked glycosylation recognition sequence (Asn X Ser/Thr) was changed in each case to the structurally similar Gln (CAG or CAA) such that two nucleotide changes in the codon would be required for reversion Replication of one triple mutant (g456), however, was severely impaired A revertant of the g456 mutant was recovered form CEMx174 cells with a Met-to-Val compensatory substitution at position 144, 2 amino acids upstream of attachment site 5 Thus, a debilitating loss of sites for N-linked glycosylation can be compens ated for by amino acid changes not involving the Asn-X-Ser/Thr consensus motif These results provide a framework to begin testing the hypothesis that carbohydrates form a barrier that can limit the humoral immune responses to the virus PUBLICATIONS Reitter, JN and Desrosiers, RC Identification of a replication-competent strains of simian immunodeficiency virus lacking multiple attachment sites for n-linked carbohydrates in variable regions 1 and 2 of the surface envelope protein J Virol 1998; 72:5399-5407

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000168-41
Application #
6591301
Study Section
Project Start
2002-05-01
Project End
2003-04-30
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
41
Fiscal Year
2002
Total Cost
$111,112
Indirect Cost
Name
Harvard University
Department
Type
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115
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