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Nef Enhances HIV-1 Replication and Infectivity Independently of SERINC5 in CEM T Cells

Overview
Journal Virology
Specialty Microbiology
Date 2022 Dec 28
PMID 36577173
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Abstract

A primary function of HIV-1 Nef is the enhancement of viral infectivity and replication. Whether counteraction of the antiretroviral proteins SERINC3 and SERINC5 is the cause of this positive influence on viral growth-rate and infectivity remains unclear. Here, we utilized CRISPR/Cas9 to knockout SERINC3 and SERINC5 in a leukemic CD4-positive T cell line (CEM) that displays nef-related infectivity and growth-rate phenotypes. Viral replication was attenuated in CEM cells infected with HIV-1 lacking Nef (HIV-1ΔNef). This attenuated growth-rate phenotype was observed regardless of whether the coding regions of the serinc3 or serinc5 genes were intact. Moreover, knockout of serinc5 alone or of both serinc5 and serinc3 together failed to restore the infectivity of HIV1ΔNef virions produced from infected CEM cells. Our results corroborate a similar study using another T-lymphoid cell line (MOLT-3) and indicate that the antagonism of SERINC3 and SERINC5 does not fully explain the virology of HIV-1 lacking Nef.

Citing Articles

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References
1.
Spina C, Kwoh T, Chowers M, Guatelli J, Richman D . The importance of nef in the induction of human immunodeficiency virus type 1 replication from primary quiescent CD4 lymphocytes. J Exp Med. 1994; 179(1):115-23. PMC: 2191324. DOI: 10.1084/jem.179.1.115. View

2.
Crotti A, Neri F, Corti D, Ghezzi S, Heltai S, Baur A . Nef alleles from human immunodeficiency virus type 1-infected long-term-nonprogressor hemophiliacs with or without late disease progression are defective in enhancing virus replication and CD4 down-regulation. J Virol. 2006; 80(21):10663-74. PMC: 1641799. DOI: 10.1128/JVI.02621-05. View

3.
Ross T, Oran A, Cullen B . Inhibition of HIV-1 progeny virion release by cell-surface CD4 is relieved by expression of the viral Nef protein. Curr Biol. 1999; 9(12):613-21. DOI: 10.1016/s0960-9822(99)80283-8. View

4.
Wallace J, Kagele D, Eiring A, Kim C, Hu R, Runtsch M . miR-155 promotes FLT3-ITD-induced myeloproliferative disease through inhibition of the interferon response. Blood. 2017; 129(23):3074-3086. PMC: 5465836. DOI: 10.1182/blood-2016-09-740209. View

5.
Noviello C, Benichou S, Guatelli J . Cooperative binding of the class I major histocompatibility complex cytoplasmic domain and human immunodeficiency virus type 1 Nef to the endosomal AP-1 complex via its mu subunit. J Virol. 2007; 82(3):1249-58. PMC: 2224416. DOI: 10.1128/JVI.00660-07. View