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A Recombinant Vaccinia Virus Encoding the Interferon‐Inducible T‐Cell Alpha Chemoattractant is Attenuated In Vivo
Author(s) -
Hamilton N. H. R.,
Mahalingam S.,
Banyer J. L.,
Ramshaw I. A.,
Thomson S. A.
Publication year - 2004
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.0300-9475.2004.01391.x
Subject(s) - vaccinia , virus , virology , biology , chemokine , interferon , immune system , mononuclear cell infiltration , orthopoxvirus , poxviridae , recombinant virus , microbiology and biotechnology , recombinant dna , immunology , gene , biochemistry
Abstract 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‐γ (IFN‐γ). 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.