Affiliation:
1. Division of Virology, Paul-Ehrlich-Institut, D-63255 Langen, Germany
2. Institute of Virology, Technical University of Munich/Helmholtz Zentrum München, D-81675 Munich, Germany
3. Institute for Clinical Chemistry, Hannover Medical School, D-30625 Hannover, Germany
Abstract
ABSTRACT
Orthopoxviruses commonly enter into humans and animals via the respiratory tract. Herein, we show that immigration of leukocytes into the lung is triggered via intranasal infection of mice with modified vaccinia virus Ankara (MVA) and not with the vaccinia virus (VACV) Elstree, Wyeth, or Western Reserve (WR) strain. Immigrating cells were identified as monocytes, neutrophils, and CD4
+
lymphocytes by flow cytometry and could be detected 24 h and 48 h postinfection. Using an in vitro chemotaxis assay, we confirmed that infection with MVA induces the expression of a soluble chemotactic factor for monocytes, identified as CCL2 (monocyte chemotactic protein-1 [MCP-1]). In contrast to infection with several other VACV strains, MVA induced the expression of CCL2, CCL3, CCL4, and CXCL10 in the human monocytic cell line THP-1 as well as in primary human monocytes. Thus, MVA, and not the VACV Elstree, Wyeth, or WR strain, consistently triggered the expression of a panel of chemokines, including CCL2, in the murine lung, correlating considerably with the immigration of leukocytes. Using CCL2-deficient mice, we demonstrate that CCL2 plays a key role in MVA-triggered respiratory immigration of leukocytes. Moreover, UV irradiation of MVA prevented CCL2 expression in vitro and in vivo as well as respiratory immigration of leukocytes, demonstrating the requirement for an activated molecular viral life cycle. We propose that MVA-triggered chemokine expression causes early immigration of leukocytes to the site of infection, a feature that is important for rapid immunization and its safety and efficiency as a viral vector.
Publisher
American Society for Microbiology
Subject
Virology,Insect Science,Immunology,Microbiology
Reference52 articles.
1. Alcami, A., J. A. Symons, P. D. Collins, T. J. Williams, and G. L. Smith. 1998. Blockade of chemokine activity by a soluble chemokine binding protein from vaccinia virus. J. Immunol.160:624-633.
2. Auwerx, J. 1991. The human leukemia cell line, THP-1: a multifacetted model for the study of monocyte-macrophage differentiation. Experientia47:22-31.
3. Benda, R., and L. Danes. 1969. The role of alveolar macrophages in inhalation infection of rabbits with vaccinia virus. II. Experiments with medium and small doses of virus. Acta Virol.13:527-531.
4. Broder, C. C., P. E. Kennedy, F. Michaels, and E. A. Berger. 1994. Expression of foreign genes in cultured human primary macrophages using recombinant vaccinia virus vectors. Gene142:167-174.
5. Poxvirus pathogenesis
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