Impact of glycosylation on antigenicity of simian immunodeficiency virus SIV239: induction of rapid V1/V2-specific non-neutralizing antibody and delayed neutralizing antibody following infection with an attenuated deglycosylated mutant.
Infection of rhesus macaques with a deglycosylation mutant, Delta5G, derived from SIV239, a pathogenic clone of simian immunodeficiency virus (SIV), led to robust acute-phase viral replication followed by a chronic phase with undetectable viral load. This study examined whether humoral responses in Delta5G-infected animals played any role in the control of infection. Neutralizing antibodies (nAbs) were elicited more efficiently in Delta5G-infected animals than in SIV239-infected animals. However, functional nAb measured by 90% neutralization was prominent in only two of the five Delta5G-infected animals, and only at 8 weeks post-infection (p.i.), when viral loads were already below 10(4) copies ml(-1). These results suggest a minimal role for nAbs in the control of the primary infection. In contrast, whilst Ab responses to epitopes localized to the variable loops V1/V2 were detected in all Delta5G-infected animals at 3 weeks p.i., this response was associated with a concomitant reduction in Ab responses to epitopes in gp41 compared with those in SIV239-infected animals. These results suggest that the altered surface glycosylation and/or conformation of viral spikes induce a humoral response against SIV that is distinct from the response induced by SIV239. More interestingly, whereas V1/V2-specific Abs were induced in all animals, these Abs were associated with vigorous Delta5G-specific virion capture ability in only two Delta5G-infected animals that exhibited a functional nAb response. Thus, whereas the deglycosylation mutant infection elicited early virion capture and subsequent nAbs, the responses differed among animals, suggesting the existence of host factors that may influence the functional humoral responses against human immunodeficiency virus/SIV.
Sugimoto
Chie
C
CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan.|Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Tsukuba, Ibaraki 305-0843, Japan.|AIDS Research Center, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan.
Nakayama
Emi E
EE
Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
Shioda
Tatsuo
T
Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
Villinger
Francois
F
Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA.
Ansari
Aftab A
AA
Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA.
Yamamoto
Naoki
N
AIDS Research Center, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan.
Suzuki
Yasuo
Y
Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Kasugai, Aichi 487-8501, Japan.|CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan.
Nagai
Yoshiyuki
Y
Center of Research Network for Infectious Diseases, Riken, Chiyoda-ku, Tokyo 100-0006, Japan.
Mori
Kazuyasu
K
CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan.|Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Tsukuba, Ibaraki 305-0843, Japan.|AIDS Research Center, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan.
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology; D015686:Gene Products, env / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D006031:Glycosylation; D008253:Macaca mulatta / Q000276:immunology* / Q000821:virology; D009500:Neutralization Tests; D018449:SAIDS Vaccines / Q000276:immunology; D015302:Simian Immunodeficiency Virus / Q000145:classification / Q000235:genetics / Q000276:immunology*; D014766:Viremia / Q000276:immunology / Q000821:virology
D000914:Antibodies, Viral; D000956:Antigens, Viral; D015686:Gene Products, env; D018449:SAIDS Vaccines