Open AccessA Spread-Deficient Cytomegalovirus for Assessment of First-Target Cells in Vaccination
Author(s) -
Hermine Mohr,
Jurica Arapović,
Hermine Mühlbach,
Marc Panzer,
Annelies Weyn,
Lars Dölken,
Astrid Krmpotić,
David Voehringer,
Zsolt Ruzsics,
Ulrich H. Koszinowski,
Torsten Sacher
Publication year - 2010
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.02696-09
Subject(s) - biology , immunogenicity , tropism , virology , human cytomegalovirus , vaccination , cd8 , immunization , genome , tissue tropism , immune system , gene , immunology , virus , genetics
Human cytomegalovirus (HCMV) is a human pathogen that causes severe disease primarily in the immunocompromised or immunologically immature individual. To date, no vaccine is available. We describe use of a spread-deficient murine CMV (MCMV) as a novel approach for betaherpesvirus vaccination. To generate a spread-deficient MCMV, the conserved, essential geneM94 was deleted. Immunization with MCMV-ΔM94 is apathogenic and protective against wild-type challenge even in highly susceptible IFNαβR−/− mice. MCMV-ΔM94 was able to induce a robust CD4+ and CD8+ T-cell response as well as a neutralizing antibody response comparable to that induced by wild-type infection. Endothelial cells were identified as activators of CD8+ T cellsin vivo . Thus, the vaccination with a spread-deficient betaherpesvirus is a safe and protective strategy and allows the linkage between cell tropism and immunogenicity. Furthermore, genomes of MCMV-ΔM94 were present in lungs 12 months after infection, revealing first-target cells as sites of genome maintenance.