@article{16ccdddae7bf4cb9a7dbe6977c8f23de,
title = "Replication of HIV-1 envelope protein cytoplasmic domain variants in permissive and restrictive cells",
abstract = "Wild type (WT) HIV-1 envelope (Env) protein cytoplasmic tails (CTs) appear to be composed of membrane-proximal, N-terminal unstructured regions, and three C-terminal amphipathic helices. Previous studies have shown that WT and CT-deleted (ΔCT) Env proteins are incorporated into virus particles via different mechanisms. WT Env proteins traffic to cell plasma membranes (PMs), are rapidly internalized, recycle to PMs, and are incorporated into virions in permissive and restrictive cells in a Gag matrix (MA) protein-dependent fashion. In contrast, previously described ΔCT proteins do not appear to be internalized after their arrival to PMs, and do not require MA, but are only incorporated into virions in permissive cell lines. We have analyzed a new set of HIV-1 CT variants with respect to their replication in permissive and restrictive cells. Our results provide novel details as to how CT elements regulate HIV-1 Env protein function.",
keywords = "Cytoplasmic tail, Envelope protein, HIV-1, Replication",
author = "Staubus, {August O.} and Ayna Alfadhli and Barklis, {Robin Lid} and Eric Barklis",
note = "Funding Information: We thank Drs. David Kabat and Bruce Chesebro respectively for supplying the HiJ and Hy183 cell lines. The Chessie 8, CEM-SS and MT-4 cell lines were obtained from NIH Aids Reagent Program, and the anti-gp41(MPER) 2F5 antibody was kindly supplied by Dr. Hermann Katinger (Polymun Scientific). We are grateful for help, advice, and assistance from Logan Harper, Andrew Mack, Roland Max Petty, Christopher Ritchie, and Fikadu Tafesse. This research was supported by NIH grant R01 GM060170 . Funding Information: In a subsequent infection experiment (Fig. 3C-D), WT and 716AAAX viruses again were tested, along with the 716Ins virus. Not surprisingly, the WT virus again replicated well in both MT-4 and CEM-SS cells, while the 716AAAX virus was defective. The 716Ins virus showed a different phenotype. In particular, 716Ins demonstrated a slight replication delay in MT-4 cells (Fig. 3C), but a 50 day delay in CEM-SS cells (Fig. 3D). To ascertain whether these late-replicating viruses might be revertants, they were collected, designated as putative revertant (716Ins-R) stocks, normalized to WT, 716Ins parental, and 813X truncation virus stocks, and used to infect new MT4 and CEM-SS cells (Fig. 4A-B). In these infections, 813X and parental 716Ins viruses showed similar phenotypes, with slightly delayed replication kinetics in MT-4 cells, and no replication in CEM-SS cells. However, the 716Ins-R stock replicated at the WT rate in MT-4 cells (Fig. 4A), and at only a slightly delayed rate in CEM-SS cells (Fig. 4B), strongly supporting the idea that the 716Ins-R stock contained revertant viruses.We thank Drs. David Kabat and Bruce Chesebro respectively for supplying the HiJ and Hy183 cell lines. The Chessie 8, CEM-SS and MT-4 cell lines were obtained from NIH Aids Reagent Program, and the anti-gp41(MPER) 2F5 antibody was kindly supplied by Dr. Hermann Katinger (Polymun Scientific). We are grateful for help, advice, and assistance from Logan Harper, Andrew Mack, Roland Max Petty, Christopher Ritchie, and Fikadu Tafesse. This research was supported by NIH grant R01 GM060170. Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",
year = "2019",
month = dec,
doi = "10.1016/j.virol.2019.09.008",
language = "English (US)",
volume = "538",
pages = "1--10",
journal = "Virology",
issn = "0042-6822",
publisher = "Academic Press Inc.",
}