An arthritogenic alphavirus uses the alpha1beta1 integrin collagen receptor.
Ross River (RR) virus is an alphavirus endemic to Australia and New Guinea and is the aetiological agent of epidemic polyarthritis or RR virus disease. Here we provide evidence that RR virus uses the collagen-binding alpha1beta1 integrin as a cellular receptor. Infection could be inhibited by collagen IV and antibodies specific for the beta1 and alpha1 integrin proteins, and fibroblasts from alpha1-integrin-/- mice were less efficiently infected than wild-type fibroblasts. Soluble alpha1beta1 integrin bound immobilized RR virus, and peptides representing the alpha1beta1 integrin binding-site on collagen IV inhibited virus binding to cells. We speculate that two highly conserved regions within the cell-receptor binding domain of E2 mimic collagen and provide access to cellular collagen-binding receptors.
La Linn
May
M
The Australian Centre for International and Tropical Health and Nutrition, Brisbane, Queensland, Australia.
Eble
Johannes A
JA
Lübken
Christoph
C
Slade
Robert W
RW
Heino
Jyrki
J
Davies
Janet
J
Suhrbier
Andreas
A
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D024141:Collagen Type IV / Q000494:pharmacology; D005347:Fibroblasts; D006367:HeLa Cells; D006801:Humans; D039423:Integrin alpha1 / Q000235:genetics / Q000276:immunology; D039222:Integrin alpha1beta1 / Q000737:chemistry / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D018342:Receptors, Adrenergic, beta-1 / Q000276:immunology; D011991:Receptors, Virus / Q000737:chemistry / Q000502:physiology*; D012398:Ross River virus / Q000502:physiology*; D012995:Solubility; D014779:Virus Replication / Q000187:drug effects
D000906:Antibodies; D024141:Collagen Type IV; D039423:Integrin alpha1; D039222:Integrin alpha1beta1; D018342:Receptors, Adrenergic, beta-1; D011991:Receptors, Virus