title: Contrasting antibody responses to intrasubtype superinfection with CRF02_AG.
abstract: HIV superinfection describes the sequential infection of an individual with two or more unrelated HIV strains. Intersubtype superinfection has been shown to cause a broader and more potent heterologous neutralizing antibody response when compared to singly infected controls, yet the effects of intrasubtype superinfection remain controversial. Longitudinal samples were analyzed phylogenetically for pol and env regions using Next-Generation Sequencing and envelope cloning. The impact of CRF02_AG intrasubtype superinfection was assessed for heterologous neutralization and antibody binding responses. We compared two cases of CRF02_AG intrasubtype superinfection that revealed complete replacement of the initial virus by superinfecting CRF02_AG variants with signs of recombination. NYU6564, who became superinfected at an early time point, exhibited greater changes in antibody binding profiles and generated a more potent neutralizing antibody response post-superinfection compared to NYU6501. In contrast, superinfection occurred at a later time point in NYU6501 with strains harboring significantly longer V1V2 regions with no observable changes in neutralization patterns. Here we show that CRF02_AG intrasubtype superinfection can induce a cross-subtype neutralizing antibody response, and our data suggest timing and/or superinfecting viral envelope characteristics as contributing factors. These results highlight differential outcomes in intrasubtype superinfection and provide the first insight into cases with CRF02_AG, the fourth most prevalent HIV-1 strain worldwide.
authors.affiliation: Department of Microbiology, New York University School of Medicine, New York, NY, United States of America.
authors.forename: Colleen R
authors.initials: CR
authors.lastname: Courtney
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, NY, United States of America.
authors.forename: Luzia
authors.initials: L
authors.lastname: Mayr
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, NY, United States of America.
authors.forename: Aubin J
authors.initials: AJ
authors.lastname: Nanfack
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, NY, United States of America.|Faculty of Medicine and Biomedical Sciences, University of Yaoundé, Yaoundé, Cameroon.
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Banin
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, NY, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Tuen
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY, United States of America.
authors.forename: Ruimin
authors.initials: R
authors.lastname: Pan
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY, United States of America.
authors.forename: Xunqing
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY, United States of America.
authors.forename: Xiang-Peng
authors.initials: XP
authors.lastname: Kong
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States of America.
authors.forename: Allison R
authors.initials: AR
authors.lastname: Kirkpatrick
authors.affiliation: Genomics Unit, Research Technologies Branch, Rocky Mountain Laboratories, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, United States of America.
authors.forename: Daniel
authors.initials: D
authors.lastname: Bruno
authors.affiliation: Genomics Unit, Research Technologies Branch, Rocky Mountain Laboratories, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, United States of America.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Martens
authors.affiliation: Genomics Unit, Research Technologies Branch, Rocky Mountain Laboratories, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, United States of America.
authors.forename: Lydia
authors.initials: L
authors.lastname: Sykora
authors.affiliation: Genomics Unit, Research Technologies Branch, Rocky Mountain Laboratories, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, United States of America.
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Porcella
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States of America.|Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, United States of America.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Redd
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States of America.|Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, United States of America.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Quinn
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, NY, United States of America.|Veterans Affairs New York Harbor Healthcare Systems, New York, NY, United States of America.
authors.forename: Phillipe N
authors.initials: PN
authors.lastname: Nyambi
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, NY, United States of America.
authors.forename: Ralf
authors.initials: R
authors.lastname: Dürr
mesh_terms: D057134:Antibodies, Neutralizing; D000917:Antibody Formation; D000939:Epitopes / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D010802:Phylogeny; D011247:Pregnancy; D011995:Recombination, Genetic; D015163:Superinfection / Q000821:virology*; D019562:Viral Load; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000235:genetics
chemical_list: D057134:Antibodies, Neutralizing; D000939:Epitopes; D054299:env Gene Products, Human Immunodeficiency Virus; D054302:pol Gene Products, Human Immunodeficiency Virus