University of Massachusetts Medical School Faculty Publications
UMMS Affiliation
Program in Molecular Medicine; Graduate School of Biomedical Sciences
Publication Date
2019-09-24
Document Type
Article Preprint
Disciplines
Amino Acids, Peptides, and Proteins | Microbiology | Viruses
Abstract
Host plasma membrane protein SERINC5 is incorporated into budding retrovirus particles where it blocks subsequent entry into susceptible target cells. Three accessory proteins encoded by diverse retroviruses, HIV-1 Nef, EIAV S2, and MLV Glycogag, each independently disrupt SERINC5 antiviral activity, by redirecting SERINC5 from the site of virion assembly on the plasma membrane to an internal RAB7+ endosomal compartment. Pseudotyping retroviruses with particular glycoproteins, e.g., the vesicular stomatitis glycoprotein (VSV G), renders the infectivity of particles resistant to inhibition by virion-associated SERINC5. To better understand viral determinants for SERINC5-sensitivity, the effect of SERINC5 was assessed using HIV-1, MLV, and M-PMV virion cores, pseudotyped with glycoproteins from Arenavirus, Coronavirus, Filovirus, Rhabdovirus, Paramyxovirus, and Orthomyxovirus genera. Infectivity of particles, pseudotyped with HIV-1, amphotropic-MLV, or influenza virus glycoproteins, was decreased by SERINC5, whether the core was provided by HIV-1, MLV, or M-PMV. Particles generated by all three cores, and pseudotyped with glycoproteins from either avian leukosis virus-A, human endogenous retrovirus K (HERV-K), ecotropic-MLV, HTLV-1, Measles morbillivirus, lymphocytic choriomeningitis mammarenavirus (LCMV), Marburg virus, Ebola virus, severe acute respiratory syndrome-related coronavirus (SARS-CoV), or VSV, were insensitive to SERINC5. In contrast, particles pseudotyped with M-PMV, RD114, or rabies virus (RABV) glycoproteins were sensitive to SERINC5, but only with particular retroviral cores. Resistance to SERINC5 by particular glycoproteins did not correlate with reduced SERINC5 incorporation into particles or with the route of viral entry. These findings indicate that some non-retroviruses may be sensitive to SERINC5 and that, in addition to the viral glycoprotein, the retroviral core influences sensitivity to SERINC5.
Keywords
microbiology, SERINC5, retrovirus
Rights and Permissions
The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-NC-ND 4.0 International license.
DOI of Published Version
10.1101/780577
Source
bioRxiv 780577; doi: https://doi.org/10.1101/780577. Link to preprint on bioRxiv service.
Journal/Book/Conference Title
bioRxiv
Repository Citation
Diehl WE, Guney MH, Kyawe PP, University of Virginia, University of Trento, Luban J. (2019). Influence of different glycoproteins and of the virion core on SERINC5 antiviral activity. University of Massachusetts Medical School Faculty Publications. https://doi.org/10.1101/780577. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/1689
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.