title: Human immunodeficiency virus type 1 variants isolated from single plasma samples display a wide spectrum of neutralization sensitivity.
abstract: Individuals infected with human immunodeficiency virus type 1 (HIV-1) harbor a mixture of viral variants with different sequences and in some instances with different phenotypic properties. Major and rapid fluctuations in the proportion of viral variants coexisting in an infected individual can be observed under strong pharmacological and immune selective pressure. Because of the short half-life of HIV-infected cells and of HIV virions in the blood, plasma virus populations are highly relevant to HIV evolution in the face of these selective pressures. Here we analyzed the sensitivity to antibody-mediated neutralization of viral variants coexisting in the plasma virus populations of two infected patients. For each patient, several replication-competent viral clones were constructed that carry primary envelope gene sequences obtained from a single plasma sample. Viral clones differed in their tropism and replicative capacity and in the number and positions of glycosylation sites in the envelope glycoproteins. Viruses were tested against heterologous and autologous sera obtained at different time points. Interestingly, we found that viral variants coexisting in each plasma sample were highly heterogeneous in terms of sensitivity to neutralization. The order of sensitivity depended on the serum used and was not associated with virus tropism. The neutralization potency of sera increased with the duration of the infection for both autologous and heterologous neutralization.
authors.affiliation: INSERM U552 Recherche Antivirale, Paris, France.
authors.forename: Katharina
authors.initials: K
authors.lastname: Skrabal
authors.forename: Sentob
authors.initials: S
authors.lastname: Saragosti
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Labernardière
authors.forename: Francis
authors.initials: F
authors.lastname: Barin
authors.forename: François
authors.initials: F
authors.lastname: Clavel
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Mammano
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D004279:DNA, Viral / Q000235:genetics; D015752:Genes, env; D014644:Genetic Variation; D015483:HIV Antibodies / Q000097:blood; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology; D015700:HIV Envelope Protein gp41 / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000235:genetics* / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010802:Phylogeny; D017386:Sequence Homology, Amino Acid; D014766:Viremia / Q000276:immunology / Q000821:virology
chemical_list: D004279:DNA, Viral; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41