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Mammalian host cells permissive for vaccinia infection represent a broad category of cells capable of supporting the complete life cycle of the vaccinia virus (VACV), a member of the Orthopoxvirus genus. Unlike many viruses that require specific high-affinity receptors, vaccinia exhibits an exceptionally wide host range by utilizing ubiquitous cell surface molecules, such as glycosaminoglycans and integrins, to trigger entry via macropinocytosis or plasma membrane fusion (Mercer & Helenius, 2008, Science). Within these permissive cells, the virus establishes 'viral factories' in the cytoplasm, hijacking host ribosomes and metabolic pathways to produce progeny (McFadden, 2005, Nature Reviews Microbiology). These cells are not a single therapeutic target but rather the biological substrate for infection; however, they are essential for evaluating the efficacy of antivirals like tecovirimat and brincidofovir. Research into these cells focuses on identifying host factors that facilitate viral assembly and the mechanisms by which the virus evades the host's innate immune responses. Antiviral intervention typically involves targeting viral enzymes within these cells, such as the DNA polymerase or the VP37 envelope protein (Grosenbach et al., 2018, NEJM). The permissivity of these cells is also a critical factor in the use of vaccinia as a vector for vaccines and oncolytic therapy.
Antiviral drugs typically target viral proteins within these cells rather than the host cells themselves; for example, tecovirimat inhibits the viral VP37 envelope wrapping protein (encoded by the F13L gene) to prevent the formation of egress-competent enveloped virions, while cidofovir and brincidofovir inhibit the viral DNA polymerase to halt genome replication (Grosenbach et al., 2018, NEJM; De Clercq, 2002, Clinical Microbiology Reviews).
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