Chapter Poxvirus Infections. Goldsmith L. Lowell A. Goldsmith, et al. Fitzpatrick's Dermatology in General Medicine, 8e. McGraw Hill; Accessed November 14, McGraw Hill. Download citation file: RIS Zotero. Reference Manager. Autosuggest Results. Print Poxviruses at a Glance Poxviruses are the largest animal viruses; they can cause disease of varying severity in humans.
Smallpox is the only poxvirus for which humans are the sole reservoir, which allowed its eradication. The smallpox vaccine virus, vaccinia, has its own adverse effects. Monkeypox is a zoonotic infection endemic in Africa, but it has recently appeared in the Western Hemisphere. Milker's nodule and orf mainly cause localized cutaneous infections.
Molluscum contagiosum is generally a benign cutaneous disease most frequently seen in children and immunocompromised individuals.
Sixth, there are many poxviruses, including replicating and non-replicating ones in humans and other animals, allowing researchers to choose the most applicable. Seventh, poxviruses are stable, grow very fast, and can be produced at high titers for large scale manufacture. Lastly, when used in oncolytic therapy, poxvirus infection can stimulate anti-tumor immunity [ 65 ], which is critical to removing cancer cells. Poxviruses began to be employed as vaccine vectors almost four decades ago in the early s when several groups pioneered their use to express foreign antigens [ 66 , 67 , 68 , 69 , 70 , 71 , 72 ].
Since then, a number of veterinary vaccines based on different poxviruses have been commercially licensed, including the rabies vaccine. Rabies virus infection of humans is deadly, and most transmissions are through bites from infected animals.
Recombinant vaccinia virus expressing rabies virus glycoprotein G has been successfully used to eliminate rabies from wildlife in some Western European countries [ 73 , 74 , 75 , 76 , 77 , 78 , 79 ]. In addition, ALVAC is a canarypox virus-based vector system, which has been used to develop several veterinary vaccines such as canine distemper virus, rabies virus, and equine influenza virus [ 80 , 81 ].
Another veterinary vaccine, Trovac AI H5, is a fowlpox virus-based avian influenza virus vaccine expressing the avian influenza viral H5 antigen, which has been used in the United States and Central America [ 82 ].
Many more poxvirus-based vaccines are under investigation. These have shown promising effects in mice and macaques [ 84 , 85 , 86 , 87 ]. With further research, it is expected that poxvirus vector-based vaccines will be licensed for humans, which requires substantially increasing the investments and efforts to understand the fundamental aspects of poxvirus replication, as well as collaboration among poxvirologists, immunologists, clinicians, and veterinarians. Oncolytic virotherapy is a targeted cancer therapy using viruses to infect and destroy cancer cells.
While the idea to use viruses to treat cancers has been of interest to medical doctors for over a century, only in the past few decades has it become a highly promising and rapidly developing area. A growing number of patients benefit from this oncolytic therapy [ 88 ]. There are a number of viruses with diverse characteristics in development to treat many kinds of cancers and poxviruses are among the most promising candidates for oncolytic actions.
While several members of poxviruses from different genera Orthopoxvirus, Leporipoxvirus, and Yatapoxvirus have been the target of development, most research in the past decade has been focused on vaccinia virus Orthopoxvirus and myxoma virus Leporipoxvirus [ 90 , 91 , 92 , 93 , 94 , 95 ]. JX was developed based on a modified vaccinia Copenhagen strain with deletion of viral thymidine kinase gene and insertion of granulocyte monocyte colony-stimulating factor GM-CSF , which aimed to improve the ability of the virus to target and lyse cancer cells with specificity and stimulate anti-tumor immune responses.
It was the first vaccinia virus-based oncolytic therapy that was tested in clinical trials starting with melanoma patients and was later engineered to combat other types of cancers [ 96 , 97 , 98 , 99 , , , , ]. More vaccinia virus strains have been developed and are in various stages of clinical or pre-clinical trials to treat hepatocellular carcinoma, pediatric solid tumors, lung cancer, etc.
Interestingly, a non-replicating, inactivated modified vaccinia Ankara MVA has also been shown to have oncolytic potential [ 65 ], which would enhance the safety profiling of vaccinia virus-based oncolytic therapy. Another poxvirus with great potential in oncolytic research is myxoma virus [ 93 , ]. However, studies have found that this virus can infect and kill non-rabbit cancer cells, including human cancer cells.
This implies a robust safety profile for myxoma virus as it does not seem to do any harm, even to immunocompromised mice [ 93 ]. More development of poxviruses to fight different cancers in humans and animals is anticipated. Another critical aspect is to understand the functions of poxvirus genes in modulating the tumor microenvironment and anti-tumor immunity, which will allow genetic engineering of poxviruses to enhance their oncolytic specificity, potency, and safety profile.
The poxvirus family includes many members that are pathogenic to humans and animals and pose significant risk to public health and economic activity. Understanding this large family of viruses, including their epidemiology, transmission, ecology, molecular biology, replication mechanisms, and strategies to take over the host cells, is the most critical task for developing the means to diagnose, treat, and manage these viruses; along with preventing future outbreaks.
It is of note that almost all of these aspects of poxviruses are under-studied, and many questions remain unanswered. Poxviruses also possess tremendous scientific value for understanding life processes and cellular biology, thanks to their large genomes, complex virions, and life cycle. The utility of poxviruses in fighting other infectious diseases and cancers also has great potential. Improved understanding of this family of viruses will provide the foundation for genetically engineering them as better vaccine- and gene-delivery vectors and oncolytic agents.
Figure 2 illustrates the aspects the author believes are critical in understating poxviruses and their utilities. Damon IK. Fields Virology, vol.
Lippincott; Moss B. Poxviridae: the viruses and their replication. Fields virology, vol. Google Scholar. Genome sequence diversity and clues to the evolution of variola smallpox virus. PubMed Article Google Scholar. Hopkins, DR. Ramses V: earliest know victim?. World Health, p. Smallpox and its eradication. Geneva: World Health Organization; Crosby AW Kiple, pp — Cambridge: Cambridge University Press.
Henderson DA. The eradication of smallpox—an overview of the past, present, and future. Edwardes EJ. A concise history of small-pox and vaccination in Europe. London: H. Lewis; Chang CF. Disease and its impact on politics, diplomacy, and the military: the case of smallpox and the Manchus — J Hist Med Allied Sci.
Fenner F. The global eradication of smallpox. Med J Aust. Construction of an infectious horsepox virus vaccine from chemically synthesized DNA fragments. McCarthy M. Smallpox samples are found in FDA storage room in Maryland. Protecting our forces: improving vaccine acquisition and availability in the U. Hoy SM. Tecovirimat: first global approval. Specific targeting of the F13L protein by ST affects orthopoxvirus production differently.
Antivir Ther. A review of compounds exhibiting anti-orthopoxvirus activity in animal models. Antiviral Res. Cidofovir inhibits genome encapsidation and affects morphogenesis during the replication of vaccinia virus. J Virol. Andrei G, Snoeck R. Cidofovir activity against poxvirus infections. The efficacy of cidofovir treatment of mice infected with ectromelia mousepox virus encoding interleukin The spectre of smallpox lingers. Nature ; Institution of Medicine. The incidence of molluscum contagiosum among American Indians and Alaska Natives.
While some poxviruses, such as smallpox variola virus , no longer exist in nature, other poxviruses can still cause disease. These include monkeypox virus, orf virus, molluscum contagiosum, and others. Smallpox is a serious, contagious, and sometimes fatal infectious disease. There is no specific treatment for smallpox disease, and the only prevention is vaccination.
The last naturally occurring case in the world was in Somalia in But most experts believe that numerous stocks exist around the world, whether in clandestine labs or preserved in human tissue , such as the scabs used for immunizations against smallpox into the twentieth century.
A similarly forgotten stock of smallpox was found in a lab in Eastern Europe in the s, for instance, and more recently at the former Swiss Serum and Vaccine Institute in Bern, says Peter Jahrling, a virologist at the National Institute of Allergy and Infectious Diseases in Frederick, Maryland. And those are only the stocks that officials know about: Jahrling says that he found out about the latest discovery when White House officials were discussing how to notify the WHO.
He says that in the past, the response to such discoveries would probably have been simply to heat the virus to very high temperatures to kill it. But the case is unusual, Damon says, because the vials were stored in a cold unit instead of in a liquid nitrogen freezer, as the official stocks are. The NIH says that it plans to conduct a comprehensive search of all its laboratory spaces as soon as possible.
But such a move may not be sufficient to find other forgotten stocks, if they exist, says Jahrling, because disorganized scientists could have squirrelled samples away in unexpected places decades ago.
You can also search for this author in PubMed Google Scholar. Infectious diseases: Smallpox watch Apr WHO to decide fate of smallpox stocks May
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