Glycosylphosphatidylinositol Anchor Deficiency Attenuates the Production of Infectious HIV-1 and Renders Virions Sensitive to Complement Attack

Tohti Amet, Jie Lan, Nicole Shepherd, Kai Yang, Daniel Byrd, Yanyan Xing, Andy Yu

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Human immunodeficiency virus type 1 (HIV-1) escapes complement-mediated lysis (CML) by incorporating host regulators of complement activation (RCA) into its envelope. CD59, a key member of RCA, is incorporated into HIV-1 virions at levels that protect against CML. Since CD59 is a glycosylphosphatidylinositol-anchored protein (GPI-AP), we used GPI anchor-deficient Jurkat cells (Jurkat-7) that express intracellular CD59, but not surface CD59, to study the molecular mechanisms underlying CD59 incorporation into HIV-1 virions and the role of host proteins in virus replication. Compared to Jurkat cells, Jurkat-7 cells were less supportive to HIV-1 replication and more sensitive to CML. Jurkat-7 cells exhibited similar capacities of HIV-1 binding and entry to Jurkat cells, but were less supportive to viral RNA and DNA biosynthesis as infected Jurkat-7 cells produced reduced amounts of HIV-1 RNA and DNA. HIV-1 virions produced from Jurkat-7 cells were CD59 negative, suggesting that viral particles acquire CD59, and probably other host proteins, from the cell membrane rather than intracellular compartments. As a result, CD59-negative virions were sensitive to CML. Strikingly, these virions exhibited reduced activity of virus binding and were less infectious, implicating that GPI-APs may be also important in ensuring the integrity of HIV-1 particles. Transient expression of the PIG-A gene restored CD59 expression on the surface of Jurkat-7 cells. After HIV-1 infection, the restored CD59 was colocalized with viral envelope glycoprotein gp120/gp41 within lipid rafts, which is identical to that on infected Jurkat cells. Thus, HIV-1 virions acquire RCA from the cell surface, likely lipid rafts, to escape CML and ensure viral infectivity. Copyright Mary Ann Liebert, Inc 2016.

Original languageEnglish (US)
Pages (from-to)1100-1112
Number of pages13
JournalAIDS Research and Human Retroviruses
Volume32
Issue number10-11
DOIs
StatePublished - Nov 1 2016

Fingerprint

Glycosylphosphatidylinositols
Jurkat Cells
Virion
HIV-1
Complement Activation
Virus Attachment
Virus Replication
Glycosylphosphatidylinositol deficiency
Lipids
Virus Internalization
Viral DNA
Viral RNA
Virus Diseases
Glycoproteins
Membrane Proteins
Proteins
RNA

Keywords

  • antibody
  • complement
  • GPI-AP
  • HIV-1
  • virus binding
  • virus replication

ASJC Scopus subject areas

  • Immunology
  • Infectious Diseases
  • Virology

Cite this

Glycosylphosphatidylinositol Anchor Deficiency Attenuates the Production of Infectious HIV-1 and Renders Virions Sensitive to Complement Attack. / Amet, Tohti; Lan, Jie; Shepherd, Nicole; Yang, Kai; Byrd, Daniel; Xing, Yanyan; Yu, Andy.

In: AIDS Research and Human Retroviruses, Vol. 32, No. 10-11, 01.11.2016, p. 1100-1112.

Research output: Contribution to journalArticle

Amet, Tohti ; Lan, Jie ; Shepherd, Nicole ; Yang, Kai ; Byrd, Daniel ; Xing, Yanyan ; Yu, Andy. / Glycosylphosphatidylinositol Anchor Deficiency Attenuates the Production of Infectious HIV-1 and Renders Virions Sensitive to Complement Attack. In: AIDS Research and Human Retroviruses. 2016 ; Vol. 32, No. 10-11. pp. 1100-1112.
@article{cf58f13ad7cb4b0a8ebf05c26d4788a2,
title = "Glycosylphosphatidylinositol Anchor Deficiency Attenuates the Production of Infectious HIV-1 and Renders Virions Sensitive to Complement Attack",
abstract = "Human immunodeficiency virus type 1 (HIV-1) escapes complement-mediated lysis (CML) by incorporating host regulators of complement activation (RCA) into its envelope. CD59, a key member of RCA, is incorporated into HIV-1 virions at levels that protect against CML. Since CD59 is a glycosylphosphatidylinositol-anchored protein (GPI-AP), we used GPI anchor-deficient Jurkat cells (Jurkat-7) that express intracellular CD59, but not surface CD59, to study the molecular mechanisms underlying CD59 incorporation into HIV-1 virions and the role of host proteins in virus replication. Compared to Jurkat cells, Jurkat-7 cells were less supportive to HIV-1 replication and more sensitive to CML. Jurkat-7 cells exhibited similar capacities of HIV-1 binding and entry to Jurkat cells, but were less supportive to viral RNA and DNA biosynthesis as infected Jurkat-7 cells produced reduced amounts of HIV-1 RNA and DNA. HIV-1 virions produced from Jurkat-7 cells were CD59 negative, suggesting that viral particles acquire CD59, and probably other host proteins, from the cell membrane rather than intracellular compartments. As a result, CD59-negative virions were sensitive to CML. Strikingly, these virions exhibited reduced activity of virus binding and were less infectious, implicating that GPI-APs may be also important in ensuring the integrity of HIV-1 particles. Transient expression of the PIG-A gene restored CD59 expression on the surface of Jurkat-7 cells. After HIV-1 infection, the restored CD59 was colocalized with viral envelope glycoprotein gp120/gp41 within lipid rafts, which is identical to that on infected Jurkat cells. Thus, HIV-1 virions acquire RCA from the cell surface, likely lipid rafts, to escape CML and ensure viral infectivity. Copyright Mary Ann Liebert, Inc 2016.",
keywords = "antibody, complement, GPI-AP, HIV-1, virus binding, virus replication",
author = "Tohti Amet and Jie Lan and Nicole Shepherd and Kai Yang and Daniel Byrd and Yanyan Xing and Andy Yu",
year = "2016",
month = "11",
day = "1",
doi = "10.1089/aid.2016.0046",
language = "English (US)",
volume = "32",
pages = "1100--1112",
journal = "AIDS Research and Human Retroviruses",
issn = "0889-2229",
publisher = "Mary Ann Liebert Inc.",
number = "10-11",

}

TY - JOUR

T1 - Glycosylphosphatidylinositol Anchor Deficiency Attenuates the Production of Infectious HIV-1 and Renders Virions Sensitive to Complement Attack

AU - Amet, Tohti

AU - Lan, Jie

AU - Shepherd, Nicole

AU - Yang, Kai

AU - Byrd, Daniel

AU - Xing, Yanyan

AU - Yu, Andy

PY - 2016/11/1

Y1 - 2016/11/1

N2 - Human immunodeficiency virus type 1 (HIV-1) escapes complement-mediated lysis (CML) by incorporating host regulators of complement activation (RCA) into its envelope. CD59, a key member of RCA, is incorporated into HIV-1 virions at levels that protect against CML. Since CD59 is a glycosylphosphatidylinositol-anchored protein (GPI-AP), we used GPI anchor-deficient Jurkat cells (Jurkat-7) that express intracellular CD59, but not surface CD59, to study the molecular mechanisms underlying CD59 incorporation into HIV-1 virions and the role of host proteins in virus replication. Compared to Jurkat cells, Jurkat-7 cells were less supportive to HIV-1 replication and more sensitive to CML. Jurkat-7 cells exhibited similar capacities of HIV-1 binding and entry to Jurkat cells, but were less supportive to viral RNA and DNA biosynthesis as infected Jurkat-7 cells produced reduced amounts of HIV-1 RNA and DNA. HIV-1 virions produced from Jurkat-7 cells were CD59 negative, suggesting that viral particles acquire CD59, and probably other host proteins, from the cell membrane rather than intracellular compartments. As a result, CD59-negative virions were sensitive to CML. Strikingly, these virions exhibited reduced activity of virus binding and were less infectious, implicating that GPI-APs may be also important in ensuring the integrity of HIV-1 particles. Transient expression of the PIG-A gene restored CD59 expression on the surface of Jurkat-7 cells. After HIV-1 infection, the restored CD59 was colocalized with viral envelope glycoprotein gp120/gp41 within lipid rafts, which is identical to that on infected Jurkat cells. Thus, HIV-1 virions acquire RCA from the cell surface, likely lipid rafts, to escape CML and ensure viral infectivity. Copyright Mary Ann Liebert, Inc 2016.

AB - Human immunodeficiency virus type 1 (HIV-1) escapes complement-mediated lysis (CML) by incorporating host regulators of complement activation (RCA) into its envelope. CD59, a key member of RCA, is incorporated into HIV-1 virions at levels that protect against CML. Since CD59 is a glycosylphosphatidylinositol-anchored protein (GPI-AP), we used GPI anchor-deficient Jurkat cells (Jurkat-7) that express intracellular CD59, but not surface CD59, to study the molecular mechanisms underlying CD59 incorporation into HIV-1 virions and the role of host proteins in virus replication. Compared to Jurkat cells, Jurkat-7 cells were less supportive to HIV-1 replication and more sensitive to CML. Jurkat-7 cells exhibited similar capacities of HIV-1 binding and entry to Jurkat cells, but were less supportive to viral RNA and DNA biosynthesis as infected Jurkat-7 cells produced reduced amounts of HIV-1 RNA and DNA. HIV-1 virions produced from Jurkat-7 cells were CD59 negative, suggesting that viral particles acquire CD59, and probably other host proteins, from the cell membrane rather than intracellular compartments. As a result, CD59-negative virions were sensitive to CML. Strikingly, these virions exhibited reduced activity of virus binding and were less infectious, implicating that GPI-APs may be also important in ensuring the integrity of HIV-1 particles. Transient expression of the PIG-A gene restored CD59 expression on the surface of Jurkat-7 cells. After HIV-1 infection, the restored CD59 was colocalized with viral envelope glycoprotein gp120/gp41 within lipid rafts, which is identical to that on infected Jurkat cells. Thus, HIV-1 virions acquire RCA from the cell surface, likely lipid rafts, to escape CML and ensure viral infectivity. Copyright Mary Ann Liebert, Inc 2016.

KW - antibody

KW - complement

KW - GPI-AP

KW - HIV-1

KW - virus binding

KW - virus replication

UR - http://www.scopus.com/inward/record.url?scp=84991340853&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84991340853&partnerID=8YFLogxK

U2 - 10.1089/aid.2016.0046

DO - 10.1089/aid.2016.0046

M3 - Article

C2 - 27231035

AN - SCOPUS:84991340853

VL - 32

SP - 1100

EP - 1112

JO - AIDS Research and Human Retroviruses

JF - AIDS Research and Human Retroviruses

SN - 0889-2229

IS - 10-11

ER -