Abstract
BackgroundVaccinia virus, the prototype member of the family Poxviridae, was used extensively in the past as the Smallpox vaccine, and is currently considered as a candidate vector for new recombinant vaccines. Vaccinia virus has a wide host range, and is known to infect cultures of a variety of cell lines of mammalian origin. However, little is known about the virus tropism in human leukocyte populations. We report here that various cell types within leukocyte populations have widely different susceptibility to infection with vaccinia virus.ResultsWe have investigated the ability of vaccinia virus to infect human PBLs by using virus recombinants expressing green fluorescent protein (GFP), and monoclonal antibodies specific for PBL subpopulations. Flow cytometry allowed the identification of infected cells within the PBL mixture 1–5 hours after infection. Antibody labeling revealed that different cell populations had very different infection rates. Monocytes showed the highest percentage of infected cells, followed by B lymphocytes and NK cells. In contrast to those cell types, the rate of infection of T lymphocytes was low. Comparison of vaccinia virus strains WR and MVA showed that both strains infected efficiently the monocyte population, although producing different expression levels. Our results suggest that MVA was less efficient than WR in infecting NK cells and B lymphocytes. Overall, both WR and MVA consistently showed a strong preference for the infection of non-T cells.ConclusionsWhen infecting fresh human PBL preparations, vaccinia virus showed a strong bias towards the infection of monocytes, followed by B lymphocytes and NK cells. In contrast, very poor infection of T lymphocytes was detected. These finding may have important implications both in our understanding of poxvirus pathogenesis and in the development of improved smallpox vaccines.
Highlights
Vaccinia virus, the prototype member of the family Poxviridae, was used extensively in the past as the Smallpox vaccine, and is currently considered as a candidate vector for new recombinant vaccines
Where adequate marker molecules for different cell populations exist, this approach should facilitate the study of the susceptibility of cell types to vaccinia virus infection
A marked preference was noted for the infection of non-T cells, since green fluorescent protein (GFP) positive cells amounted to 19% of non-T lymphocytes, while only 1.9% of T cells were infected
Summary
The prototype member of the family Poxviridae, was used extensively in the past as the Smallpox vaccine, and is currently considered as a candidate vector for new recombinant vaccines. Vaccinia virus has a wide host range, and is known to infect cultures of a variety of cell lines of mammalian origin. We report here that various cell types within leukocyte populations have widely different susceptibility to infection with vaccinia virus. Well characterized in vitro, little is known about the ability of vaccinia virus to infect different cell types in vivo. Vaccinia virus host range in cell culture is known to be determined by several genes. Virology Journal 2004, 1:10 http://www.virologyj.com/content/1/1/10 recent years by the growing use of the Modified Vaccinia Ankara (MVA) virus strain, whose replication is severely impaired in human cells [2,3,4]. Genes known to influence the ability of vaccinia virus to infect cells, termed host range genes, have been identified, and shown to block productive infection at different points in the replication cycle. MVA replication of non-permissive cells proceeds through early and late gene expression, but is blocked at late times in a step of virion morphogenesis [5]
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