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Viruses 2018, 10(9), 493; https://doi.org/10.3390/v10090493

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

Department of Microbiology and Immunology, The University of Western Ontario, Schulich School of Medicine and Dentistry, London, ON N6A 5C1, Canada
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Received: 20 July 2018 / Revised: 30 August 2018 / Accepted: 11 September 2018 / Published: 13 September 2018
(This article belongs to the Special Issue CSV2018: The 2nd symposium of the Canadian Society for Virology (CSV))
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Abstract

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. View Full-Text
Keywords: human immunodeficiency virus; Nef; diversity; subtypes; microscopy human immunodeficiency virus; Nef; diversity; subtypes; microscopy
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Van Nynatten, L.R.; Johnson, A.L.; Dirk, B.S.; Pawlak, E.N.; Jacob, R.A.; Haeryfar, S.M.M.; Dikeakos, J.D. Identification of Novel Subcellular Localization and Trafficking of HIV-1 Nef Variants from Reference Strains G (F1.93.HH8793) and H (BE.93.VI997). Viruses 2018, 10, 493.

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