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A SIV molecular clone that targets the CNS and induces neuroAIDS in rhesus macaques.
Matsuda, Kenta; Riddick, Nadeene E; Lee, Cheri A; Puryear, Sarah B; Wu, Fan; Lafont, Bernard A P; Whitted, Sonya; Hirsch, Vanessa M.
Afiliação
  • Matsuda K; Laboratory of Molecular Microbiology, NIAID, NIH, Bethesda, MD, United States of America.
  • Riddick NE; Laboratory of Molecular Microbiology, NIAID, NIH, Bethesda, MD, United States of America.
  • Lee CA; Laboratory of Molecular Microbiology, NIAID, NIH, Bethesda, MD, United States of America.
  • Puryear SB; Laboratory of Molecular Microbiology, NIAID, NIH, Bethesda, MD, United States of America.
  • Wu F; Laboratory of Molecular Microbiology, NIAID, NIH, Bethesda, MD, United States of America.
  • Lafont BAP; Viral Immunology Section, OD, NIAID, NIH, Bethesda, MD, United States of America.
  • Whitted S; Laboratory of Molecular Microbiology, NIAID, NIH, Bethesda, MD, United States of America.
  • Hirsch VM; Laboratory of Molecular Microbiology, NIAID, NIH, Bethesda, MD, United States of America.
PLoS Pathog ; 13(8): e1006538, 2017 Aug.
Article em En | MEDLINE | ID: mdl-28787449
ABSTRACT
Despite effective control of plasma viremia with the use of combination antiretroviral therapies (cART), minor cognitive and motor disorders (MCMD) persist as a significant clinical problem in HIV-infected patients. Non-human primate models are therefore required to study mechanisms of disease progression in the central nervous system (CNS). We isolated a strain of simian immunodeficiency virus (SIV), SIVsm804E, which induces neuroAIDS in a high proportion of rhesus macaques and identified enhanced antagonism of the host innate factor BST-2 as an important factor in the macrophage tropism and initial neuro-invasion of this isolate. In the present study, we further developed this model by deriving a molecular clone SIVsm804E-CL757 (CL757). This clone induced neurological disorders in high frequencies but without rapid disease progression and thus is more reflective of the tempo of neuroAIDS in HIV-infection. NeuroAIDS was also induced in macaques co-inoculated with CL757 and the parental AIDS-inducing, but non-neurovirulent SIVsmE543-3 (E543-3). Molecular analysis of macaques infected with CL757 revealed compartmentalization of virus populations between the CNS and the periphery. CL757 exclusively targeted the CNS whereas E543-3 was restricted to the periphery consistent with a role for viral determinants in the mechanisms of neuroinvasion. CL757 would be a useful model to investigate disease progression in the CNS and as a model to study virus reservoirs in the CNS.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Síndrome de Imunodeficiência Adquirida dos Símios / Complexo AIDS Demência / Vírus da Imunodeficiência Símia / Modelos Animais de Doenças Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Síndrome de Imunodeficiência Adquirida dos Símios / Complexo AIDS Demência / Vírus da Imunodeficiência Símia / Modelos Animais de Doenças Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2017 Tipo de documento: Article