Display options
Share it on

J Virol. 2021 Feb 03; doi: 10.1128/JVI.02355-20. Epub 2021 Feb 03.

Structural Domains of the Herpes Simplex Type 1 gD Protein that Restrict HIV-1 Particle Infectivity.

Journal of virology

Sachith Polpitiya Arachchige, Wyatt Henke, Maria Kalamvoki, Edward B Stephens

Affiliations

  1. Department of Microbiology, Molecular Genetics and Immunology, 2000 Hixon Hall, 3901 Rainbow Blvd. University of Kansas Medical Center, Kansas City, Kansas USA 66160 Phone: 913-588-5558 Fax: 913-588-7295.
  2. Department of Microbiology, Molecular Genetics and Immunology, 2000 Hixon Hall, 3901 Rainbow Blvd. University of Kansas Medical Center, Kansas City, Kansas USA 66160 Phone: 913-588-5558 Fax: 913-588-7295 [email protected].

PMID: 33536165 PMCID: PMC8103709 DOI: 10.1128/JVI.02355-20

Abstract

Previously, we showed that the presence of the herpes simplex virus type 1 (HSV-1) gD glycoprotein but not gB potently restricted HIV-1 particle infectivity. This restriction was characterized by incorporation of HSV-1 gD and the exclusion of the HIV-1 gp120/gp41 from budding virus particles. To determine the structural domains involved in gD restriction of HIV-1, a series of deletion mutants and chimeric proteins between gD and the non-restrictive gB were generated. Our results show that deletion of the cytoplasmic tail domain (CTD) of gD or that replacement of the transmembrane domain (TMD) with the TMD from gB slightly reduced restriction activity. However, replacement of the gD CTD with that of gB resulted in lower cell surface expression, significantly less incorporation into HIV-1 particles, and inefficient restriction of the release of infectious HIV-1. Analysis of gB/gD chimeric proteins revealed that removal of the gB CTD or replacement with gD CTD resulted in enhanced surface expression and an increase in restriction activity. Finally, we show that expression of gD without other HSV-1 proteins resulted in gD fractionation into detergent resistant membranes (DRM) and that gD co-localized with the raft marker GM1, which may partially explain its incorporation into budding virus particles. Taken together, our results suggest that expression of gD at the cell surface is likely a major factor but that other intrinsic properties are also involved in the gD-mediated restriction of HIV-1 particle infectivity.

Copyright © 2021 American Society for Microbiology.

References

  1. J Virol. 2011 May;85(10):5003-15 - PubMed
  2. EMBO J. 1997 Sep 15;16(18):5501-8 - PubMed
  3. J Exp Med. 2002 Mar 4;195(5):593-602 - PubMed
  4. J Cell Biol. 1998 May 18;141(4):929-42 - PubMed
  5. PLoS Pathog. 2013;9(4):e1003278 - PubMed
  6. J Virol. 2005 Jul;79(14):8847-60 - PubMed
  7. Viruses. 2018 Nov 18;10(11): - PubMed
  8. J Biol Chem. 2001 Mar 23;276(12):9182-8 - PubMed
  9. Virology. 2007 Dec 5;369(1):105-18 - PubMed
  10. J Virol. 2004 May;78(10):5500-6 - PubMed
  11. J Virol. 2004 Jan;78(1):33-41 - PubMed
  12. J Virol. 2010 Jan;84(1):59-75 - PubMed
  13. J Mol Biol. 2011 Jul 22;410(4):582-608 - PubMed
  14. Virology. 2009 Mar 30;386(1):192-202 - PubMed
  15. J Virol. 2009 May;83(9):4060-7 - PubMed
  16. J Virol. 2003 Sep;77(17):9542-52 - PubMed
  17. J Virol. 2002 Nov;76(22):11584-95 - PubMed
  18. Trends Biochem Sci. 2015 Jul;40(7):407-18 - PubMed
  19. J Gen Virol. 2010 Sep;91(Pt 9):2145-51 - PubMed
  20. J Virol. 2000 Apr;74(8):3548-54 - PubMed
  21. J Virol. 2007 Oct;81(20):11468-78 - PubMed
  22. J Virol. 2000 Jul;74(14):6538-45 - PubMed
  23. J Virol. 2000 May;74(10):4634-44 - PubMed
  24. J Gen Virol. 2004 Dec;85(Pt 12):3517-3527 - PubMed
  25. Antimicrob Agents Chemother. 2002 Jun;46(6):1896-905 - PubMed
  26. J Virol. 2002 Sep;76(18):9271-83 - PubMed
  27. Front Biosci (Landmark Ed). 2009 Jun 01;14:5339-60 - PubMed
  28. Viruses. 2015 Sep 18;7(9):5084-114 - PubMed
  29. Virus Res. 2009 Aug;143(2):162-76 - PubMed
  30. J Virol. 2007 Dec;81(24):13889-903 - PubMed
  31. J Virol. 2007 Jul;81(14):7548-58 - PubMed
  32. AIDS Res Hum Retroviruses. 2011 Mar;27(3):239-47 - PubMed
  33. J Immunol. 2010 Jan 1;184(1):236-43 - PubMed
  34. Proc Natl Acad Sci U S A. 2016 Jan 12;113(2):E182-90 - PubMed
  35. Virology. 2000 Oct 25;276(2):289-303 - PubMed
  36. J Virol. 1999 Nov;73(11):9515-20 - PubMed
  37. Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):343-8 - PubMed
  38. J Virol. 2000 Nov;74(21):9911-5 - PubMed
  39. J Virol. 2000 Sep;74(18):8709-19 - PubMed
  40. PLoS Pathog. 2008 May 16;4(5):e1000065 - PubMed
  41. J Virol. 2008 Nov;82(21):10600-12 - PubMed
  42. Retrovirology. 2019 Apr 2;16(1):9 - PubMed
  43. Science. 1974 Feb 15;183(4125):656-7 - PubMed
  44. FASEB J. 2017 Apr;31(4):1650-1667 - PubMed
  45. Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):13925-30 - PubMed
  46. J Virol. 2018 Jan 2;92(2): - PubMed
  47. J Gen Virol. 2006 Feb;87(Pt 2):277-285 - PubMed
  48. J Virol. 1995 Jun;69(6):3824-30 - PubMed
  49. J Virol. 1993 Dec;67(12):7067-76 - PubMed
  50. J Virol. 2018 Feb 12;92(5): - PubMed
  51. Annu Rev Biochem. 2003;72:395-447 - PubMed
  52. J Virol. 2001 Apr;75(8):3675-84 - PubMed
  53. Proc Natl Acad Sci U S A. 2004 Oct 12;101(41):14889-94 - PubMed
  54. Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15936-41 - PubMed
  55. J Virol. 1995 Mar;69(3):1984-9 - PubMed
  56. J Gen Virol. 2001 Jan;82(Pt 1):215-226 - PubMed
  57. Virology. 2017 Jan 15;501:127-135 - PubMed
  58. Nat Rev Mol Cell Biol. 2000 Oct;1(1):31-9 - PubMed
  59. J Virol. 2004 Feb;78(3):1540-51 - PubMed
  60. Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13523-5 - PubMed
  61. J Virol. 2000 Apr;74(7):3264-72 - PubMed
  62. Microbes Infect. 2007 Jan;9(1):96-102 - PubMed
  63. Virology. 2005 Nov 25;342(2):215-27 - PubMed
  64. J Immunol Methods. 2002 Dec 20;271(1-2):25-35 - PubMed
  65. Nat Rev Mol Cell Biol. 2017 Jun;18(6):361-374 - PubMed
  66. Biochem J. 2009 Jan 15;417(2):525-33 - PubMed
  67. J Virol. 2003 Feb;77(3):1747-56 - PubMed
  68. Nat Rev Neurosci. 2007 Feb;8(2):128-40 - PubMed
  69. Viruses. 2015 Mar 04;7(3):915-38 - PubMed
  70. Proc Natl Acad Sci U S A. 2010 Jan 19;107(3):1190-5 - PubMed
  71. J Virol. 2009 Aug;83(16):8289-92 - PubMed
  72. J Virol. 2003 Feb;77(3):2038-45 - PubMed
  73. J Virol. 2000 Sep;74(18):8358-67 - PubMed
  74. Proc Natl Acad Sci U S A. 2015 Jun 16;112(24):7575-80 - PubMed
  75. Nature. 1997 Jun 5;387(6633):569-72 - PubMed
  76. Adv Virus Res. 2005;64:311-58 - PubMed
  77. J Virol. 2004 May;78(10):5279-87 - PubMed
  78. J Virol. 2005 Feb;79(3):1623-34 - PubMed
  79. J Virol. 2000 May;74(10):4891-3 - PubMed
  80. J Neurosci. 2003 Apr 15;23(8):3262-71 - PubMed
  81. Virology. 2002 Sep 1;300(2):244-54 - PubMed

Publication Types

Grant support