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Rapid Development of gp120-Focused Neutralizing B Cell Responses during Acute Simian Immunodeficiency Virus Infection of African Green Monkeys.
Amos, Joshua D; Himes, Jonathon E; Armand, Lawrence; Gurley, Thaddeus C; Martinez, David R; Colvin, Lisa; Beck, Krista; Overman, R Glenn; Liao, Hua-Xin; Moody, M Anthony; Permar, Sallie R.
Afiliação
  • Amos JD; Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
  • Himes JE; Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
  • Armand L; Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
  • Gurley TC; Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
  • Martinez DR; Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA.
  • Colvin L; Division of Laboratory Animal Resources, Duke University Medical Center, Durham, North Carolina, USA.
  • Beck K; Division of Laboratory Animal Resources, Duke University Medical Center, Durham, North Carolina, USA.
  • Overman RG; Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
  • Liao HX; Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
  • Moody MA; Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA Department of Immunology, Duke University Medical Center, Durham, North Carolina, USA.
  • Permar SR; Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA Department of Immunology, Duke University Medical Center, Durham, North Carolina, USA Department of Molecular Genetics and M
J Virol ; 89(18): 9485-98, 2015 Sep.
Article em En | MEDLINE | ID: mdl-26157116
UNLABELLED: The initial phases of acute human immunodeficiency virus type 1 (HIV-1) infection may be critical for development of effective envelope (Env)-specific antibodies capable of impeding the establishment of the latent pool of HIV-1-infected CD4(+) T cells, preventing virus-induced immune hyperactivation to limit disease progression and blocking vertical virus transmission. However, the initial systemic HIV-1 Env-specific antibody response targets gp41 epitopes and fails to control acute-phase viremia. African-origin, natural simian immunodeficiency virus (SIV) hosts do not typically progress to AIDS and rarely postnatally transmit virus to their infants, despite high milk viral loads. Conversely, SIV-infected rhesus macaques (RMs), Asian-origin nonnatural SIV hosts, sustain pathogenic SIV infections and exhibit higher rates of postnatal virus transmission. In this study, of acute SIV infection, we compared the initial systemic Env-specific B cell responses of AGMs and RMs in order to probe potential factors influencing the lack of disease progression observed in AGMs. AGMs developed higher-magnitude plasma gp120-specific IgA and IgG responses than RMs, whereas RMs developed more robust gp140-directed IgG responses. These gp120-focused antibody responses were accompanied by rapid autologous neutralizing responses during acute SIV infection in AGMs compared to RMs. Moreover, acute SIV infection elicited a higher number of circulating Env-specific memory B cells in peripheral blood of AGMs than in the blood of RMs. These findings indicate that AGMs have initial systemic Env-specific B cell responses to SIV infection distinct from those of a nonnatural SIV host, resulting in more functional SIV-specific humoral responses, which may be involved in impairing pathogenic disease progression and minimizing postnatal transmission. IMPORTANCE: Due to the worldwide prevalence of HIV-1 infections, development of a vaccine to prevent infection or limit the viral reservoir remains an important goal. HIV-1-infected humans, as well as SIV-infected nonnatural SIV hosts, develop pathogenic infections and readily transmit the virus to their infants. Conversely, natural SIV hosts do not develop pathogenic infections and rarely transmit the virus to their infants. The immunologic factors contributing to these favorable outcomes in natural SIV hosts could prove invaluable for directing HIV-1 vaccine and therapy design. This study identified distinctions in the specificity and function of the initial systemic SIV envelope-specific B cell response that developed during acute SIV infection in natural and nonnatural SIV host species. Identification of distinct acute B cell responses in natural SIV hosts may inform vaccine strategies seeking to elicit similar responses prior to or during the initial phases of acute HIV-1 infection.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Imunoglobulina G / Linfócitos B / Síndrome de Imunodeficiência Adquirida dos Símios / Vírus da Imunodeficiência Símia / Anticorpos Neutralizantes / Anticorpos Antivirais Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2015 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Imunoglobulina G / Linfócitos B / Síndrome de Imunodeficiência Adquirida dos Símios / Vírus da Imunodeficiência Símia / Anticorpos Neutralizantes / Anticorpos Antivirais Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2015 Tipo de documento: Article