Infection with a molecularly cloned SIVsm virus elicits high titer homologous neutralizing antibodies with heterologous neutralizing activity.
We have evaluated the homologous and heterologous neutralizing antibody response in a cohort of six Macaca nemestrina infected with the cloned virus SIVsm62d that showed different levels of envelope diversification. Two progressor macaques developed AIDS by 1.5 years post-inoculation and four non-progressors were asymptomatic for 3 years of follow-up. All macaques developed high titers of neutralizing antibodies against homologous SIVsm viruses and intermediate titers against SIVsmB670. Heterologous virus neutralization of SIVmac, SIVmne, and HIV-2 was detected at much lower levels in both progressor macaques; only one of four non-progressors had evidence for broader neutralizing antibody activity. We noted changes in potential N-linked glycosylation (PNG) sites in V1/V2, C2, and V4 that were common to multiple macaques. These results support a model for viral neutralization where heterologous neutralization is, in part, driven by a strong homologous response and may be coupled to changes in PNG sites in envelope.
Mahalanabis
M
M
Seattle Biomedical Research Institute, Seattle, WA 98109-5219, USA.
Hirsch
V M
VM
Haigwood
N L
NL
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D001483:Base Sequence; D002478:Cells, Cultured; D003001:Cloning, Molecular; D017931:DNA Primers; D006031:Glycosylation; D019302:HIV Envelope Protein gp160 / Q000235:genetics; D015498:HIV-2 / Q000235:genetics; D016013:Likelihood Functions; D008254:Macaca nemestrina; D008562:Membrane Glycoproteins / Q000235:genetics; D008957:Models, Genetic; D008969:Molecular Sequence Data; D008992:Monkey Diseases / Q000276:immunology* / Q000821:virology*; D009500:Neutralization Tests / Q000662:veterinary; D017422:Sequence Analysis, DNA / Q000662:veterinary; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000235:genetics
D000914:Antibodies, Viral; D017931:DNA Primers; D019302:HIV Envelope Protein gp160; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins; C069623:gp120 protein, Simian immunodeficiency virus