Arenavirus entry occurs through a cholesterol-dependent, non-caveolar, clathrin-mediated endocytic mechanism

Eric M. Vela, Lihong Zhang, Tonya M. Colpitts, Robert A. Davey, Judith Aronson

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Arenaviruses are important causes of viral hemorrhagic fevers in humans. Arenavirus infection of cells occurs via a pH-dependent endocytic route, but detailed studies of entry pathways have not been done. We investigated the role of cell membrane cholesterol, caveolae, and clathrin coated pits in infection by Lassa virus (LASV), which utilizes alpha-dystroglycan (α-DG) as a receptor, and Pichindé virus (PICV), which does not. Depletion of cellular cholesterol by treatment with methyl betacyclodextrin (MβCD) or nystatin/progesterone inhibited PICV replication and transfer of packaged marker gene by LASV or PICV pseudotyped retroviral particles. In cells lacking caveolae due to silencing of the caveolin-1 gene, no inhibition of PICV infection or LASV pseudotype transduction was observed. However, PICV infection and LASV and PICV pseudotype transduction was inhibited when an Eps15 dominant negative mutant was used to inhibit clathrin-mediated endocytosis. Altogether, the results indicate that diverse arenaviruses have a common requirement for cell membrane cholesterol and clathrin mediated endocytosis in establishing infection.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalVirology
Volume369
Issue number1
DOIs
StatePublished - Dec 5 2007

Fingerprint

Lassa virus
Arenavirus
Clathrin
Cholesterol
Caveolae
Virus Diseases
Endocytosis
Arenaviridae Infections
Viral Hemorrhagic Fevers
Cell Membrane
Dystroglycans
Viruses
Virus Receptors
Caveolin 1
Nystatin
Virus Replication
Infection
Genes
Progesterone

Keywords

  • Arenavirus
  • Cholesterol
  • Clathrin
  • Hemorrhagic fever
  • Lassa virus
  • Pichindé virus
  • Viral entry

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

Arenavirus entry occurs through a cholesterol-dependent, non-caveolar, clathrin-mediated endocytic mechanism. / Vela, Eric M.; Zhang, Lihong; Colpitts, Tonya M.; Davey, Robert A.; Aronson, Judith.

In: Virology, Vol. 369, No. 1, 05.12.2007, p. 1-11.

Research output: Contribution to journalArticle

Vela, Eric M. ; Zhang, Lihong ; Colpitts, Tonya M. ; Davey, Robert A. ; Aronson, Judith. / Arenavirus entry occurs through a cholesterol-dependent, non-caveolar, clathrin-mediated endocytic mechanism. In: Virology. 2007 ; Vol. 369, No. 1. pp. 1-11.
@article{06d0bef5c13a474383e9ab5afcfc78c7,
title = "Arenavirus entry occurs through a cholesterol-dependent, non-caveolar, clathrin-mediated endocytic mechanism",
abstract = "Arenaviruses are important causes of viral hemorrhagic fevers in humans. Arenavirus infection of cells occurs via a pH-dependent endocytic route, but detailed studies of entry pathways have not been done. We investigated the role of cell membrane cholesterol, caveolae, and clathrin coated pits in infection by Lassa virus (LASV), which utilizes alpha-dystroglycan (α-DG) as a receptor, and Pichind{\'e} virus (PICV), which does not. Depletion of cellular cholesterol by treatment with methyl betacyclodextrin (MβCD) or nystatin/progesterone inhibited PICV replication and transfer of packaged marker gene by LASV or PICV pseudotyped retroviral particles. In cells lacking caveolae due to silencing of the caveolin-1 gene, no inhibition of PICV infection or LASV pseudotype transduction was observed. However, PICV infection and LASV and PICV pseudotype transduction was inhibited when an Eps15 dominant negative mutant was used to inhibit clathrin-mediated endocytosis. Altogether, the results indicate that diverse arenaviruses have a common requirement for cell membrane cholesterol and clathrin mediated endocytosis in establishing infection.",
keywords = "Arenavirus, Cholesterol, Clathrin, Hemorrhagic fever, Lassa virus, Pichind{\'e} virus, Viral entry",
author = "Vela, {Eric M.} and Lihong Zhang and Colpitts, {Tonya M.} and Davey, {Robert A.} and Judith Aronson",
year = "2007",
month = "12",
day = "5",
doi = "10.1016/j.virol.2007.07.014",
language = "English (US)",
volume = "369",
pages = "1--11",
journal = "Virology",
issn = "0042-6822",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Arenavirus entry occurs through a cholesterol-dependent, non-caveolar, clathrin-mediated endocytic mechanism

AU - Vela, Eric M.

AU - Zhang, Lihong

AU - Colpitts, Tonya M.

AU - Davey, Robert A.

AU - Aronson, Judith

PY - 2007/12/5

Y1 - 2007/12/5

N2 - Arenaviruses are important causes of viral hemorrhagic fevers in humans. Arenavirus infection of cells occurs via a pH-dependent endocytic route, but detailed studies of entry pathways have not been done. We investigated the role of cell membrane cholesterol, caveolae, and clathrin coated pits in infection by Lassa virus (LASV), which utilizes alpha-dystroglycan (α-DG) as a receptor, and Pichindé virus (PICV), which does not. Depletion of cellular cholesterol by treatment with methyl betacyclodextrin (MβCD) or nystatin/progesterone inhibited PICV replication and transfer of packaged marker gene by LASV or PICV pseudotyped retroviral particles. In cells lacking caveolae due to silencing of the caveolin-1 gene, no inhibition of PICV infection or LASV pseudotype transduction was observed. However, PICV infection and LASV and PICV pseudotype transduction was inhibited when an Eps15 dominant negative mutant was used to inhibit clathrin-mediated endocytosis. Altogether, the results indicate that diverse arenaviruses have a common requirement for cell membrane cholesterol and clathrin mediated endocytosis in establishing infection.

AB - Arenaviruses are important causes of viral hemorrhagic fevers in humans. Arenavirus infection of cells occurs via a pH-dependent endocytic route, but detailed studies of entry pathways have not been done. We investigated the role of cell membrane cholesterol, caveolae, and clathrin coated pits in infection by Lassa virus (LASV), which utilizes alpha-dystroglycan (α-DG) as a receptor, and Pichindé virus (PICV), which does not. Depletion of cellular cholesterol by treatment with methyl betacyclodextrin (MβCD) or nystatin/progesterone inhibited PICV replication and transfer of packaged marker gene by LASV or PICV pseudotyped retroviral particles. In cells lacking caveolae due to silencing of the caveolin-1 gene, no inhibition of PICV infection or LASV pseudotype transduction was observed. However, PICV infection and LASV and PICV pseudotype transduction was inhibited when an Eps15 dominant negative mutant was used to inhibit clathrin-mediated endocytosis. Altogether, the results indicate that diverse arenaviruses have a common requirement for cell membrane cholesterol and clathrin mediated endocytosis in establishing infection.

KW - Arenavirus

KW - Cholesterol

KW - Clathrin

KW - Hemorrhagic fever

KW - Lassa virus

KW - Pichindé virus

KW - Viral entry

UR - http://www.scopus.com/inward/record.url?scp=35648989045&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=35648989045&partnerID=8YFLogxK

U2 - 10.1016/j.virol.2007.07.014

DO - 10.1016/j.virol.2007.07.014

M3 - Article

C2 - 17698159

AN - SCOPUS:35648989045

VL - 369

SP - 1

EP - 11

JO - Virology

JF - Virology

SN - 0042-6822

IS - 1

ER -