UMMS Affiliation

Department of Molecular, Cell and Cancer Biology

Publication Date


Document Type



Biochemistry | Immunology of Infectious Disease | Molecular Biology | Virology | Viruses


We recently identified the multipass transmembrane protein SERINC5 as an antiviral protein that can potently inhibit HIV-1 infectivity and is counteracted by HIV-1 Nef. We now report that the anti-HIV-1 activity, but not the sensitivity to Nef, is conserved among vertebrate SERINC5 proteins. However, a Nef-resistant SERINC5 became Nef sensitive when its intracellular loop 4 (ICL4) was replaced by that of Nef-sensitive human SERINC5. Conversely, human SERINC5 became resistant to Nef when its ICL4 was replaced by that of a Nef-resistant SERINC5. In general, ICL4 regions from SERINCs that exhibited resistance to a given Nef conferred resistance to the same Nef when transferred to a sensitive SERINC, and vice versa. Our results establish that human SERINC5 can be modified to restrict HIV-1 infectivity even in the presence of Nef.


HIV-1, Nef, SERINC5, restriction factor

Rights and Permissions

Copyright 2017 The Authors. This is an open access article under the CC BY-NC-ND license (

DOI of Published Version



Cell Rep. 2018 Jan 23;22(4):869-875. doi: 10.1016/j.celrep.2017.12.082. Epub 2018 Jan 28. Link to article on publisher's site

Journal/Book/Conference Title

Cell reports

Related Resources

Link to Article in PubMed

PubMed ID


Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.