Identification of Novel Subcellular Localization and Trafficking of HIV-1 Nef Variants from Reference Strains G (F1.93.HH8793) and H (BE.93.VI997)

Logan  R. Van Nynatten; Aaron  L. Johnson; Brennan  S. Dirk; Emily  N. Pawlak; Rajesh  Abraham Jacob; S.  M. Mansour Haeryfar; Jimmy  D. Dikeakos

doi:10.3390/v10090493

Viruses (Sep 2018)

Identification of Novel Subcellular Localization and Trafficking of HIV-1 Nef Variants from Reference Strains G (F1.93.HH8793) and H (BE.93.VI997)

Logan R. Van Nynatten,
Aaron L. Johnson,
Brennan S. Dirk,
Emily N. Pawlak,
Rajesh Abraham Jacob,
S. M. Mansour Haeryfar,
Jimmy D. Dikeakos

Affiliations

Logan R. Van Nynatten: Department of Microbiology and Immunology, The University of Western Ontario, Schulich School of Medicine and Dentistry, London, ON N6A 5C1, Canada
Aaron L. Johnson: Department of Microbiology and Immunology, The University of Western Ontario, Schulich School of Medicine and Dentistry, London, ON N6A 5C1, Canada
Brennan S. Dirk: Department of Microbiology and Immunology, The University of Western Ontario, Schulich School of Medicine and Dentistry, London, ON N6A 5C1, Canada
Emily N. Pawlak: Department of Microbiology and Immunology, The University of Western Ontario, Schulich School of Medicine and Dentistry, London, ON N6A 5C1, Canada
Rajesh Abraham Jacob: Department of Microbiology and Immunology, The University of Western Ontario, Schulich School of Medicine and Dentistry, London, ON N6A 5C1, Canada
S. M. Mansour Haeryfar: Department of Microbiology and Immunology, The University of Western Ontario, Schulich School of Medicine and Dentistry, London, ON N6A 5C1, Canada
Jimmy D. Dikeakos: Department of Microbiology and Immunology, The University of Western Ontario, Schulich School of Medicine and Dentistry, London, ON N6A 5C1, Canada

DOI: https://doi.org/10.3390/v10090493
Journal volume & issue: Vol. 10, no. 9
p. 493

Abstract

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The human immunodeficiency virus type 1 (HIV-1) accessory protein Nef, plays an essential role in disease progression and pathogenesis via hijacking the host cellular membrane-trafficking machinery. Interestingly, HIV-1 group-M subtypes display differences in the rate of disease progression. However, few reports investigated how the cellular behaviors and activities of Nef isolates from reference strains may differ between HIV-1 group-M subtypes. Here, we characterize how differing cellular distributions of Nef proteins across group-M subtypes may impact protein function using immunofluorescence microscopy and flow cytometric analysis. We demonstrate that Nef variants isolated from HIV-1 group-M subtypes display differences in expression, with low expressing Nef proteins from reference strains of subtypes G (F1.93.HH8793) and H (BE.93.VI997) also displaying decreased functionality. Additionally, we demonstrate variations in the subcellular distribution and localization of these Nef proteins. Nef from subtype G (F1.93.HH8793) and H (BE.93.VI997) reference strains also failed to colocalize with the trans-Golgi network, and were not differentially localized to cellular markers of multivesicular bodies or lysosomes. Strikingly, our results demonstrate that HIV-1 Nef proteins from reference strains G (F1.93.HH8793) and H (BE.93.VI997) highly colocalize with labeled mitochondrial compartments.

Published in Viruses

ISSN: 1999-4915 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Microbiology
Website: http://www.mdpi.com/journal/viruses

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