A recombinant vaccinia virus encoding the interferon-inducible T-cell alpha chemoattractant is attenuated in vivo.
Murine interferon-inducible T-cell alpha chemoattractant (I-TAC) is a potent non-ELR CXC chemokine that predominantly attracts activated T lymphocytes, binds to the receptor CXCR3 and is induced by interferon-gamma (IFN-gamma). We analysed I-TAC expression by reverse transcriptase-polymerase chain reaction during three different virus-infection models in mice, respiratory syncytial virus (RSV), influenza A and vaccinia virus western reserve (VV-WR). In the lungs from mice infected with RSV or influenza A viruses, peak expression of I-TAC coincided with peak viraemia. Surprisingly, there was no expression in the lungs of mice infected with vaccinia, unlike the elevated expression shown previously for other interferon-regulated chemokines, such as Crg2 and Mig. To further investigate the importance of this difference during vaccinia infection in mice, a recombinant virus encoding I-TAC (rVV I-TAC) was generated. Studies in C57BL/6 and Swiss nude mice showed that I-TAC expression caused increased mononuclear cell infiltration and significantly attenuated the VV. Infection of the footpads of naïve or already immune (with VV-WR) mice with either rVV I-TAC or VV-WR demonstrated that I-TAC expression reduced overall inflammation during infection and that this reduction was more pronounced in already immune mice. The data presented here show that I-TAC can have an important role during virus infections and that vaccinia has evolved ways to avoid inducing I-TAC expression.
Hamilton
N H R
NH
John Curtin School of Medical Research (JCSMR), Australian National University, Canberra, Australian Capital Territory, Australia.
Mahalingam
S
S
Banyer
J L
JL
Ramshaw
I A
IA
Thomson
S A
SA
D000818:Animals; D054371:Chemokine CXCL11; D019743:Chemokines, CXC / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D002633:Chemotaxis; D005260:Female; D005786:Gene Expression Regulation; D009980:Influenza A virus / Q000276:immunology; D008168:Lung / Q000821:virology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009976:Orthomyxoviridae Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012136:Respiratory Syncytial Viruses / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013047:Specific Pathogen-Free Organisms; D014615:Vaccinia / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology
D054371:Chemokine CXCL11; D019743:Chemokines, CXC; C515203:Cxcl11 protein, mouse; D012333:RNA, Messenger