title: HIV-1 neutralizing antibody response and viral genetic diversity characterized with next generation sequencing.
abstract: To better understand the dynamics of HIV-specific neutralizing antibody (NAb), we examined associations between viral genetic diversity and the NAb response against a multi-subtype panel of heterologous viruses in a well-characterized, therapy-naïve primary infection cohort. Using next generation sequencing (NGS), we computed sequence-based measures of diversity within HIV-1 env, gag and pol, and compared them to NAb breadth and potency as calculated by a neutralization score. Contemporaneous env diversity and the neutralization score were positively correlated (p=0.0033), as were the neutralization score and estimated duration of infection (EDI) (p=0.0038), and env diversity and EDI (p=0.0005). Neither early env diversity nor baseline viral load correlated with future NAb breadth and potency (p>0.05). Taken together, it is unlikely that neutralizing capability in our cohort was conditioned on viral diversity, but rather that env evolution was driven by the level of NAb selective pressure.
authors.affiliation: University of California San Diego, 9500 Gilman Dr. 0679, La Jolla, CA 92093, USA.
authors.forename: Christoph C
authors.initials: CC
authors.lastname: Carter
authors.affiliation: University of California San Diego, 9500 Gilman Dr. 0679, La Jolla, CA 92093, USA. Electronic address: gawagner@ucsd.edu.
authors.forename: Gabriel A
authors.initials: GA
authors.lastname: Wagner
authors.affiliation: University of California San Diego, 9500 Gilman Dr. 0679, La Jolla, CA 92093, USA.
authors.forename: George K
authors.initials: GK
authors.lastname: Hightower
authors.affiliation: Veterans Affairs San Diego Healthcare System, 3350 La Jolla Village Dr., San Diego, CA, USA.
authors.forename: Gemma
authors.initials: G
authors.lastname: Caballero
authors.affiliation: Monogram Biosciences, Inc., 345 Oyster Point Blvd, South San Francisco, CA, USA.
authors.forename: Pham
authors.initials: P
authors.lastname: Phung
authors.affiliation: University of California San Diego, 9500 Gilman Dr. 0679, La Jolla, CA 92093, USA; Veterans Affairs San Diego Healthcare System, 3350 La Jolla Village Dr., San Diego, CA, USA.
authors.forename: Douglas D
authors.initials: DD
authors.lastname: Richman
authors.affiliation: University of California San Diego, 9500 Gilman Dr. 0679, La Jolla, CA 92093, USA.
authors.forename: Sergei L Kosakovsky
authors.initials: SL
authors.lastname: Pond
authors.affiliation: University of California San Diego, 9500 Gilman Dr. 0679, La Jolla, CA 92093, USA; Veterans Affairs San Diego Healthcare System, 3350 La Jolla Village Dr., San Diego, CA, USA.
authors.forename: Davey M
authors.initials: DM
authors.lastname: Smith
mesh_terms: D057134:Antibodies, Neutralizing / Q000096:biosynthesis*; D015331:Cohort Studies; D015752:Genes, env; D015750:Genes, gag; D015751:Genes, pol; D014644:Genetic Variation; D015483:HIV Antibodies / Q000096:biosynthesis*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology*; D059014:High-Throughput Nucleotide Sequencing; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D008137:Longitudinal Studies; D013997:Time Factors
chemical_list: D057134:Antibodies, Neutralizing; D015483:HIV Antibodies
keywords: HIV-1 genetic diversity; Neutralizing antibody; Neutralizing antibody breadth and potency; Next generation sequencing; Viral evolution