Poxvirus pathogenesis

Abstract

Poxviruses are a highly successful family of pathogens, with variola virus, the causative agent of smallpox, being the most notable member. Poxviruses are unique among animal viruses in several respects. First, owing to the cytoplasmic site of virus replication, the virus encodes many enzymes required either for macromolecular precursor pool regulation or for biosynthetic processes. Second, these viruses have a very complex morphogenesis, which involves the de novo synthesis of virus-specific membranes and inclusion bodies. Third, and perhaps most surprising of all, the genomes of these viruses encode many proteins which interact with host processes at both the cellular and systemic levels. For example, a viral homolog of epidermal growth factor is active in vaccinia virus infections of cultured cells, rabbits, and mice. At least five virus proteins with homology to the serine protease inhibitor family have been identified and one, a 38-kDa protein encoded by cowpox virus, is thought to block a host pathway for generating a chemotactic substance. Finally, a protein which has homology with complement components interferes with the activation of the classical complement pathway. Poxviruses infect their hosts by all possible routes: through the skin by mechanical means (e.g., molluscum contagiosum infections of humans), via the respiratory tract (e.g., variola virus infections of humans), or by the oral route (e.g., ectromelia virus infection of the mouse). Poxvirus infections, in general, are acute, with no strong evidence for latent, persistent, or chronic infections. They can be localized or systemic. Ectromelia virus infection of the laboratory mouse can be systemic but inapparent with no mortality and little morbidity, or highly lethal with death in 10 days. On the other hand, molluscum contagiosum virus replicates only in the stratum spinosum of the human epidermis, with little or no involvement of the dermis, and does not spread systemically from the site of infection. The host response to infection is progressive and multifactorial. Early in the infection process, interferons, the alternative pathway of complement activation, inflammatory cells, and natural killer cells may contribute to slowing the spread of the infection. The cell-mediated response involving learned cytotoxic T lymphocytes and delayed-type hypersensitivity components appears to be the most important in recovery from infection. A significant role for specific antiviral antibody and antibody-dependent cell-mediated cytotoxicity has yet to be demonstrated in recovery from a primary infection, but these responses are thought to be important in preventing reinfection.

The Ocular Complications of Smallpox and Smallpox Immunization

“…Variola and vaccinia are closely related members of Orthopoxvirus, a genus of viruses within the family Poxviridae. 8 Poxviruses are large and complex brickshaped viruses consisting of a core of viral DNA, lateral bodies, an outer membrane containing tubular-shaped lipoprotein subunits, and an envelope. 9 Poxviruses use…”

Comparative Pathogenesis, Genomics and Phylogeography of Mousepox

“…The role that ATI bodies play in the life cycle of many poxviruses is unclear [28,72,73], but it has been suggested that they might be involved in viral transmission or dissemination processes [74][75][76][77][78][79]. The predicted functional differences in ECTV-H as compared to ECTV-M are restricted to two conservative amino acid changes, an insertion of a repeated amino acid motif in EVM025 and the expression of a full-length p4b protein (Table 5, Table S3).…”

Progress on Poxvirus E3 Ubiquitin Ligases and Adaptor Proteins

“…Studies have found that knocking out the BBK gene in VACV leads to a decrease in the number of mature progeny viruses ( 36 ). VACV bearing a BBK gene knockout mutation showed reduced toxicity in the nasal cavities of infected mice.…”