title: Adaptation to persistent growth in the H9 cell line renders a primary isolate of human immunodeficiency virus type 1 sensitive to neutralization by vaccine sera.
abstract: Seven diverse primary isolates of human immunodeficiency virus type 1 (HIV-1) were examined and found to be refractory to neutralization by antisera to recombinant gp120 (rgp120) protein from HIV-1 MN. This stands in marked contrast to the sensitivity exhibited by certain laboratory-adapted viruses. To understand the difference between primary and laboratory-adapted viruses, we adapted the primary virus ACH 168.10 to growth in the FDA/H9 cell line. ACH 168.10 was chosen because the V3 region of gp120 closely matches that of MN. After 4 weeks, infection became evident. The virus (168A) replicated in FDA/H9 cells with extensive cytopathic effect but was unchanged in sensitivity to antibody-mediated neutralization. Thus, growth in cell lines is not sufficient to render primary virus sensitive to neutralization. The 168A virus was, however, partially sensitive to CD4 immunoadhesin (CD4-Ig). Adaptation was continued to produce a persistently infected FDA/H9 culture that displayed minimal cytopathic effect. The virus (168C) was now sensitive to neutralization by MN rgp120 vaccine sera and by MN-specific monoclonal antibodies and showed increased sensitivity to HIVIG and CD4-Ig. 168C encoded three amino acid changes in gp120, including one within the V3 loop (I-166-->R, I-282-->N, G-318-->R). MN-specific monoclonal antibodies bound equally to the surface of cells infected with either neutralization-resistant or -sensitive virus. The coincidence of changes in neutralization sensitivity with changes in cell tropism and cytopathic effect suggests a common underlying mechanism(s) acting through the whole of the envelope protein complex.
authors.affiliation: Department of Immunology, Research Virology Laboratory, Genentech Inc., South San Francisco, California 94080.
authors.forename: T
authors.initials: T
authors.lastname: Wrin
authors.forename: T P
authors.initials: TP
authors.lastname: Loh
authors.forename: J C
authors.initials: JC
authors.lastname: Vennari
authors.forename: H
authors.initials: H
authors.lastname: Schuitemaker
authors.forename: J H
authors.initials: JH
authors.lastname: Nunberg
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology; D000222:Adaptation, Physiological; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology*; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D006168:Guinea Pigs; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000276:immunology; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D014779:Virus Replication
chemical_list: D016915:AIDS Vaccines; D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D017931:DNA Primers; D015699:HIV Envelope Protein gp120; C084715:HIV hyperimmune globulin; C082068:HIV-1 IIIB gp120 subunit vaccine; D016756:Immunoglobulins, Intravenous