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Sequential trafficking of Env and Gag to HIV-1 T cell virological synapses revealed by live imaging.
Wang, Lili; Izadmehr, Sudeh; Kamau, Edwin; Kong, Xiang-Peng; Chen, Benjamin K.
Afiliação
  • Wang L; Department of Medicine, Division of Infectious Diseases, Immunology Institute, Mount Sinai School of Medicine, New York, NY, 10029, USA.
  • Izadmehr S; Department of Medicine, Division of Infectious Diseases, Immunology Institute, Mount Sinai School of Medicine, New York, NY, 10029, USA.
  • Kamau E; Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA.
  • Kong XP; Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA.
  • Chen BK; Department of Medicine, Division of Infectious Diseases, Immunology Institute, Mount Sinai School of Medicine, New York, NY, 10029, USA. benjamin.chen@mssm.edu.
Retrovirology ; 16(1): 2, 2019 01 15.
Article em En | MEDLINE | ID: mdl-30646921
ABSTRACT

BACKGROUND:

HIV infection is enhanced by cell adhesions that form between infected and uninfected T cells called virological synapses (VS). VS are initiated by an interaction between Env and CD4 on cell surfaces and result in the recruitment of virus assembly to the site of cell-cell contact. However, the recruitment of Env to the VS and its relationship to Gag recruitment is not well defined.

RESULTS:

To study the trafficking of HIV-1 Env through the VS, we constructed a molecular clone of HIV carrying a green fluorescent protein-Env fusion protein called, HIV Env-isfGFP-∆V1V2. The Env-isfGFP-∆V1V2 fusion protein does not produce virus particles on its own, but can be rescued by cotransfection with full-length HIV constructs and produce virus particles that package the fluorescent Env. These rescued fluorescent Env can participate in VS formation and can be used to directly image CD4-dependent Env transfer across VS from donor to target cells. The movements of fluorescently tagged Gag and Env to the VS and transfer into target cells can be also tracked through live imaging. Time lapse live imaging reveals evidence of limited Env accumulation at the site of cell-cell contact shortly after cell adhesion, followed by Gag re-distribution to contact area. Both Gag and Env can be recruited to form button-like spots characteristic of VS.

CONCLUSIONS:

Env and Gag are recruited to the VS in a coordinated temporal sequence and subsequently transfer together across the synapse into the target cell. Env accumulations, when observed, are earlier than Gag re-distribution to the contact area during formation of VS.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfócitos T CD4-Positivos / Adesão Celular / HIV-1 / Montagem de Vírus / Produtos do Gene gag do Vírus da Imunodeficiência Humana / Produtos do Gene env do Vírus da Imunodeficiência Humana / Microscopia Intravital Limite: Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfócitos T CD4-Positivos / Adesão Celular / HIV-1 / Montagem de Vírus / Produtos do Gene gag do Vírus da Imunodeficiência Humana / Produtos do Gene env do Vírus da Imunodeficiência Humana / Microscopia Intravital Limite: Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article