title: Effects of neutralizing antibodies on escape from CD8+ T-cell responses in HIV-1 infection.
abstract: Despite substantial advances in our knowledge of immune responses against HIV-1 and of its evolution within the host, it remains unclear why control of the virus eventually breaks down. Here, we present a new theoretical framework for the infection dynamics of HIV-1 that combines antibody and CD8(+) T-cell responses, notably taking into account their different lifespans. Several apparent paradoxes in HIV pathogenesis and genetics of host susceptibility can be reconciled within this framework by assigning a crucial role to antibody responses in the control of viraemia. We argue that, although escape from or progressive loss of quality of CD8(+) T-cell responses can accelerate disease progression, the underlying cause of the breakdown of virus control is the loss of antibody induction due to depletion of CD4(+) T cells. Furthermore, strong antibody responses can prevent CD8(+) T-cell escape from occurring for an extended period, even in the presence of highly efficacious CD8(+) T-cell responses.
authors.affiliation: Department of Zoology, University of Oxford, Oxford OX1 3PS, UK.
authors.forename: Paul S
authors.identifier: http://orcid.org/0000-0002-9318-2581
authors.initials: PS
authors.lastname: Wikramaratna
authors.affiliation: Department of Zoology, University of Oxford, Oxford OX1 3PS, UK.
authors.forename: José
authors.initials: J
authors.lastname: Lourenço
authors.affiliation: Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7BN, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Klenerman
authors.affiliation: Department of Zoology, University of Oxford, Oxford OX1 3PS, UK.
authors.forename: Oliver G
authors.identifier: http://orcid.org/0000-0002-8797-2667
authors.initials: OG
authors.lastname: Pybus
authors.affiliation: Department of Zoology, University of Oxford, Oxford OX1 3PS, UK sunetra.gupta@zoo.ox.ac.uk.
authors.forename: Sunetra
authors.initials: S
authors.lastname: Gupta
mesh_terms: D057134:Antibodies, Neutralizing; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018450:Disease Progression; D015483:HIV Antibodies; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D006801:Humans; D057131:Immune Evasion; D018448:Models, Immunological; D009154:Mutation; D014766:Viremia / Q000276:immunology / Q000821:virology
chemical_list: D057134:Antibodies, Neutralizing; D015483:HIV Antibodies
keywords: AIDS; HIV; T-cell escape; mathematical model; neutralizing antibodies