Lymphocytic choriomeningitis virus uses a novel endocytic pathway for infectious entry via late endosomes.
The endocytic entry of lymphocytic choriomeningitis virus (LCMV) into host cells was compared to the entry of viruses known to exploit clathrin or caveolae/raft-dependent pathways. Pharmacological inhibitors, expression of pathway-specific dominant-negative constructs, and siRNA silencing of clathrin together with electron and light microscopy provided evidence that although a minority population followed a classical clathrin-mediated mechanism of entry, the majority of these enveloped RNA viruses used a novel endocytic route to late endosomes. The pathway was clathrin, dynamin-2, actin, Arf6, flotillin-1, caveolae, and lipid raft independent but required membrane cholesterol. Unaffected by perturbation of Rab5 or Rab7 and apparently without passing through Rab5/EEA1-positive early endosomes, the viruses reached late endosomes and underwent acid-induced penetration. This membrane trafficking route between the plasma membrane and late endosomes may function in the turnover of a select group of surface glycoproteins such as the dystroglycan complex, which serves as the receptor of LCMV.
Institute of Biochemistry, ETH Zurich, Schafmattstrasse 18, CH-8093 Zurich, Switzerland.
Katharina
K
Quirin
Bruno
B
Eschli
Isabella
I
Scheu
Linda
L
Poort
Jürgen
J
Kartenbeck
Ari
A
Helenius
D000818:Animals; D002522:Chlorocebus aethiops; D002784:Cholesterol / Q000378:metabolism*; D002966:Clathrin / Q000235:genetics / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology*; D011992:Endosomes / Q000821:virology*; D006367:HeLa Cells; D006801:Humans; D008217:Lymphocytic choriomeningitis virus / Q000472:pathogenicity*; D021962:Membrane Microdomains / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D014709:Vero Cells
D002966:Clathrin; D034741:RNA, Small Interfering; D002784:Cholesterol