Vaccinia virus poxvirus

Section Navigation. Facebook Twitter LinkedIn Syndicate. Signs and Symptoms. Minus Related Pages. Although the potential re-emergence of smallpox as a consequence of deliberate bioterrorism has been the subject of intense speculation, the appearance of any pathogenic poxvirus that spreads efficiently from human-to-human would be considered an immediate public health crisis.

The human monkeypox outbreak in the United States illustrates how vulnerable the human population is to the emergence and re-emergence of viral pathogens from unsuspected sources. In the case of poxviruses, we know little about the features that govern the species tropism of poxvirus—host relationships, or the hurdles that need to be overcome to initiate zoonotic poxvirus infections in non-evolutionary hosts. The best available evidence indicates that poxviruses bind to and enter mammalian cells promiscuously, but their ability to complete the complex cytoplasmic replication cycle that is needed to generate progeny virus, and then to spread successfully to a new host, can vary markedly between cells of different lineages and host species.

On the basis of our current knowledge, all the main determinants of poxvirus tropism at the cellular level are intracellular events that take place downstream of virus binding and entry. Although signals from specific sentinel host-cell receptors can probably regulate subsequent poxvirus replication, it seems that poxviruses do not require specific host-cell receptors for virus adsorption and fusion events, for the efficient internalization of the virus core structure or for the initiation of early transcription.

Rather, the main features that functionally regulate subsequent events in the infected cell are the requirement for various trans -acting factors from the host cell and the ability to inhibit diverse cellular antiviral responses such as apoptosis and the interferon pathway. Also, the ultimate outcome of a given infection is potently influenced by the unique portfolio of immunomodulatory and host-range genes that give each poxvirus unique properties of host range, pathogenesis and the potential for host-to-host spread.

As more information is gathered about the molecular basis for tropism determinants of poxviruses, it is likely that new strategies will be uncovered to experimentally manipulate the natural species barriers that regulate zoonotic infections. This knowledge will facilitate the engineering of poxviruses as safer vectors for vaccines and gene therapy, and as tissue-targeted oncolytic viruses to treat human neoplasms.

However, the sobering conclusion remains that even if the final stocks of variola virus are destroyed, the potential for the emergence of other poxvirus-derived human pathogens remains. Hopefully, as the general principles that govern poxvirus tropism and host range are better understood, we will also be better prepared to respond to other zoonotic virus infections.

The help of D. Hall in preparing the manuscript and the critical feedback from M. Stanford and M. Barry are gratefully appreciated. He currently serves on numerous grants panels, committees, organizations and editorial boards, and his professional interest is in immuno-evasion strategies of viruses. Cowpox virus. Ectromelia virus. Poxvirus Bioinformatics Resouce Center. WHO smallpox slide set. Grant McFadden's laboratory.

I am co-founder of a biotechnology company VIRON Therapeutics which is developing anti-inflammatory proteins derived from viruses. However, the corporate agenda for this company is unrelated to this particular review. National Center for Biotechnology Information , U. Nat Rev Microbiol. Grant McFadden. Author information Copyright and License information Disclaimer.

Grant McFadden, Email: ac. This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. This article has been cited by other articles in PMC.

Abstract Despite the success of the WHO-led smallpox eradication programme a quarter of a century ago, there remains considerable fear that variola virus, or other related pathogenic poxviruses such as monkeypox, could re-emerge and spread disease in the human population.

Main Despite remarkable advances in the control and treatment of infectious diseases, the problem of emerging and re-emerging pathogens is likely to be one of the main issues of medical and public health in the twenty-first century 1. Table 1 Examples of poxvirus host ranges.

Open in a separate window. Figure 1. Examples of host-restricted poxviruses. Figure 2. All poxviruses are morphologically similar. Figure 3. Poxvirus replication cycle. Figure 4. Intracellular signalling events modulate poxvirus tropism. Table 3 Poxvirus host-range genes.

Figure 5. Origin of modified vaccinia Ankara strain. Surface receptors that are pattern-recognition sentinels for recognizing pathogen infection and inducing innate antimicrobial responses. They participate in the recognition of pathogens and initiate the early phases of the host antiviral responses. Poxviruses are the only viruses to express active members of this superfamily.

By contrast, T H 2 immune responses are skewed towards the activation of humoral patyhways, especially antibodies. Competing interests I am co-founder of a biotechnology company VIRON Therapeutics which is developing anti-inflammatory proteins derived from viruses. References 1. The challenge of emerging and re-emerging infectious diseases.

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Dissociation of progeny vaccinia virus from the cell membrane is regulated by a viral envelope glycoprotein? Vaccinia virus envelope H3L protein binds to cell surface heparan sulfate and is important for intracellular mature virion morphogenesis and virus infection in vitro and in vivo.

Vaccinia envelope D8L protein binds to cell surface chondroitin sulfate and mediates intracellular mature virions adsorption to cells.

A27L protein mediates vaccinia virus interaction with cell surface heparan sulfate. Cell surface proteoglycans are necessary for A27L protein-mediated cell fusion: identification of the N-terminal region of A27L protein as the glycosaminoglycan-binding domain. Vaccinia virus entry into cells is dependent on a virion surface protein encoded by the A28L gene.

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A vaccinia virus late transcription factor copurifies with a factor that binds to a viral late promoter and is complemented by extracts from uninfected HeLa cells. The smallpox vaccine does not contain the smallpox virus and it cannot cause smallpox. The different strains of vaccinia virus used in research and clinical settings present different levels of risk.

Laboratory-acquired poxvirus infections of most concern are from the orthopoxviruses that infect humans: variola virus causes smallpox; human-specific , monkeypox virus causes smallpox-like disease , cowpox virus causes skin pustule, generalized rash , and vaccinia virus causes skin pustule, systemic illness. There have been 18 significant reported vaccinia laboratory infections and 2 reported infections of laboratory workers with recombinant vaccinia virus over the past 30 years. Symptoms Vaccinia causes a virus disease of skin induced by inoculation for the prevention of smallpox — vesicular or pustular lesion, area of induration or erythema surrounding a scab or ulcer at inoculation site.

The clinical picture resembles influenza, and days after fever subsides, a rash can develop with lesions containing infectious virus. These lesions can happen on the face, extremities, palms and soles, then trunk. Lesions progress through stages as following: macules, papules, vesicles, pustules, then crusted scabs. Incubation Period Incubation period is days; commonly days to onset of illness and additional days to onset of rash.

Period of communicability:. Personal protective equipment includes but is not limited to gowns with tight wrists and ties in back, disposable gloves, combination safety glass and mask or a face shield.

Recombinant Vaccinia vectors: Vaccinia virus can accept as much as 25 kb of foreign DNA, making it useful for expressing large eukaryotic and prokaryotic genes. Foreign genes are integrated stably into the viral genome, resulting in efficient replication and expression of biologically active molecules. Furthermore, posttranslational modifications e.

Vaccinia is used to generate live recombinant vaccines for the treatment of other illnesses.