TY - JOUR
T1 - Tracking global patterns of N-linked glycosylation site variation in highly variable viral glycoproteins
T2 - HIV, SIV, and HCV envelopes and influenza hemagglutinin
AU - Zhang, Ming
AU - Gaschen, Brian
AU - Blay, Wendy
AU - Foley, Brian
AU - Haigwood, Nancy
AU - Kuiken, Carla
AU - Korber, Bette
N1 - Funding Information:
We thank Drs. John Moore and Julie Overbaugh for helpful discussions and Dennis Bruton for asking the questions lead to this study. This work was supported by the NIH-DOE interagency agreement for the HIV-1 sequence and immunology database project YI-AI-1500-03 (M.Z., B.G., B.F., C.K., B.K.), a Los Alamos National Laboratory research development award (B.K. and B.G.), and NIH-PHS grants AI-26503 (N.H.) and AI-34251 (N.H.). W.B. is supported by a University of Washington Center for AIDS Research fellowship (AI-27757).
PY - 2004/12
Y1 - 2004/12
N2 - Human and simian immunodeficiency viruses (HIV and SIV), influenza virus, and hepatitis C virus (HCV) have heavily glycosylated, highly variable surface proteins. Here we explore N-linked glycosylation site (sequon) variation at the population level in these viruses, using a new Web-based program developed to facilitate the sequon tracking and to define patterns (www.hiv.lanl.gov). This tool allowed rapid visualization of the two distinctive patterns of sequon variation found in HIV-1, HIV-2, and SIV CPZ. The first pattern (fixed) describes readily aligned sites that are either simply present or absent. These sites tend to be occupied by high-mannose glycans. The second pattern (shifting) refers to sites embedded in regions of extreme local length variation and is characterized by shifts in terms of the relative position and local density of sequons; these sites tend to be populated by complex carbohydrates. HIV, with its extreme variation in number and precise location of sequons, does not have a net increase in the number of sites over time at the population level. Primate lentiviral lineages have host species-dependent levels of sequon shifting, with HIV-1 in humans the most extreme. HCV E1 and E2 proteins, despite evolving extremely rapidly through point mutation, show limited sequon variation, although two shifting sites were identified. Human influenza A hemagglutinin H3 HA1 is accumulating sequons over time, but this trend is not evident in any other avian or human influenza A serotypes.
AB - Human and simian immunodeficiency viruses (HIV and SIV), influenza virus, and hepatitis C virus (HCV) have heavily glycosylated, highly variable surface proteins. Here we explore N-linked glycosylation site (sequon) variation at the population level in these viruses, using a new Web-based program developed to facilitate the sequon tracking and to define patterns (www.hiv.lanl.gov). This tool allowed rapid visualization of the two distinctive patterns of sequon variation found in HIV-1, HIV-2, and SIV CPZ. The first pattern (fixed) describes readily aligned sites that are either simply present or absent. These sites tend to be occupied by high-mannose glycans. The second pattern (shifting) refers to sites embedded in regions of extreme local length variation and is characterized by shifts in terms of the relative position and local density of sequons; these sites tend to be populated by complex carbohydrates. HIV, with its extreme variation in number and precise location of sequons, does not have a net increase in the number of sites over time at the population level. Primate lentiviral lineages have host species-dependent levels of sequon shifting, with HIV-1 in humans the most extreme. HCV E1 and E2 proteins, despite evolving extremely rapidly through point mutation, show limited sequon variation, although two shifting sites were identified. Human influenza A hemagglutinin H3 HA1 is accumulating sequons over time, but this trend is not evident in any other avian or human influenza A serotypes.
KW - Immune escape
KW - N-linked glycosylation
KW - Neutralization antibody
KW - Variability
KW - Virus
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U2 - 10.1093/glycob/cwh106
DO - 10.1093/glycob/cwh106
M3 - Review article
C2 - 15175256
AN - SCOPUS:9744280420
SN - 0959-6658
VL - 14
SP - 1229
EP - 1246
JO - Glycobiology
JF - Glycobiology
IS - 12
ER -