Usage of integrin and heparan sulfate as receptors for mouse adenovirus type 1.
Adenovirus fiber knobs are the capsid components that interact with binding receptors on cells, while an Arg-Gly-Asp (RGD) sequence usually found in the penton base protein is important for the interaction of most adenoviruses with integrin entry receptors. Mouse adenovirus type 1 (MAV-1) lacks an RGD sequence in the virion penton base protein. We tested whether an RGD sequence found in the MAV-1 fiber knob plays a role in infection. Treatment of cells with a competitor RGD peptide or a purified recombinant RGD-containing fiber knob prior to infection resulted in reduced virus yields compared to those of controls, indicating the importance of the RGD sequence for infection. An investigation of the role of integrins as possible receptors showed that MAV-1 yields were reduced in the presence of EDTA, an inhibitor of integrin binding, and in the presence of anti-alpha(v) integrin antibody. Moreover, mouse embryo fibroblasts that were genetically deficient in alpha(v) integrin yielded less virus, supporting the hypothesis that alpha(v) integrin is a likely receptor for MAV-1. We also investigated whether glycosaminoglycans play a role in MAV-1 infection. Preincubation of MAV-1 with heparin, a heparan sulfate glycosaminoglycan analog, resulted in a decrease in MAV-1 virus yields. Reduced MAV-1 infectivity was also found with cells that genetically lack heparan sulfate or cells that were treated with heparinase I. Cumulatively, our data demonstrate that the RGD sequence in the MAV-1 fiber knob plays a role in infection by MAV-1, alpha(v) integrin acts as a receptor for the virus, and cell surface heparin sulfate glycosaminoglycans are important in MAV-1 infection.
Raman
Sharmila
S
Department of Microbiology and Immunology, University of Michigan, Michigan 48109-5620, USA.
Hsu
Tien-Huei
TH
Ashley
Shanna L
SL
Spindler
Katherine R
KR
D000256:Adenoviridae / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D036022:Capsid Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D005347:Fibroblasts / Q000821:virology; D006497:Heparan Sulfate / Q000172:deficiency / Q000378:metabolism*; D016023:Integrins / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D011991:Receptors, Virus / Q000378:metabolism*; D016415:Sequence Alignment; D053585:Virus Attachment
D036022:Capsid Proteins; D006497:Heparan Sulfate; D016023:Integrins; D011991:Receptors, Virus; C018315:hexon capsid protein, Adenovirus