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A unique historical commentary from a One Health perspective… “What’s in a name?”  Plenty! Provided to One Health Initiative website www.onehealthinitiative.com April 9, 2015 by: Jan Clement, MD, Hantavirus Reference Centre, Laboratory of Clinical and Epidemiological Virology & Rega Institute for Medical Research, University of Leuven, U.Z. Gasthuisberg, Herestraat, 49 B-300 Leuven, Belgium (Tel: + 32-16-347908; Fax +32-16-347900; e-mail jan.clement@uzleuven.be) John P. Woodall, PhD, Nucleus for the Investigation of Emerging Infectious Diseases, Institute of Medical Biochemistry, Center for Health Sciences, Federal University of Rio de Janeiro, Brazil (e-mail: woodall@promedmail.org) Charles H. Calisher, PhD, Arthropod-borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, 3195 Rampart Rd., Foothills Campus, Fort Collins, Colorado, U.S.A. 80523-1690 (e-mail: calisher@cybersafe.net)   “… in 1970, British veterinarians in Uganda sent 699 cattle ticks to the East African Virus Research Institute, from which a strain (AMP 10358) of Congo virus was isolated. These findings suggested that ticks could be vectors of the virus to humans and that livestock might constitute at least hosts if not reservoirs of this newly recognized hemorrhagic fever virus.  In May 1973, Greek veterinarians isolated AP 92 virus from ticks feeding on goats in Vergina, northern Greece.  Moreover they showed that AP 92 virus clearly reacted in immunodiffusion tests with the same goats’ sera.  In the same study they demonstrated that AP 92 virus reacted in the same way with Russian antisera to Crimean hemorrhagic fever virus and with antisera to Congo virus, provided by Chumakov and Casals, respectively.  Casals’ paradigm was thereby confirmed.  In subsequent years demonstrations of the relatedness of AP 92 and several other Crimean-Congo hemorrhagic fever viruses from Greece and surrounding countries allowed an increasing “One Health approach” to studies of this emerging virus.”   Words are the primary means by which we communicate with each other.  Use the wrong word, misuse a pause or a punctuation mark, and you might be misunderstood.  Viral taxonomists are particularly fussy about such things.  Viral taxonomists have conjured up rules and traditions to follow and most investigators adhere to such rules, which have been published by the International Committee on Taxonomy of Viruses (ICTV; http://www.ictvonline.org/).  However, some, by ignorance or arrogance, unintentionally re-invent taxonomy by misnaming their little friends.  This has caused complications and confusions that have had to be addressed.  The intent of this paper is to present three interesting examples of such misnamings, the problems thereby caused, and the possible solutions to those problems.  Reading this One Health Initiative website www.onehealthinitiative.com and/or the One Health Newsletter http://epi.ufl.edu/onehealth/news/one-health-newsletter/ is or should be important to physicians, veterinarians, osteopaths and others in health and environmentally related disciplines who intend to publish or to scan the scientific literature. Crimean–Congo hemorrhagic fever virus: Although a similar disease had been reported at least 800 years earlier in what is now Tajikistan, beginning in 1944 Russian scientists were first to record the clinical aspects of Crimean hemorrhagic fever (CHF) and in 1947 demonstrated that it had a viral etiology in 200 Russian soldiers appointed by the Russian authorities to harvest crops during wartime in the Crimea instead of the local peasants, who had been driven away.  However, due to this unexpected and previously non-scheduled military activity, these soldiers had to sleep outdoors, were fed upon by ticks, and shortly afterwards many suffered a severe hemorrhagic fever, thus named CHF. In 1945, inoculation of “volunteers” with filtered suspensions of ticks and with tissues of these CHF patients proved that CHF was caused by a tick-transmitted virus (1).  However, Russian scientists were unable to isolate the virus.  It was not until 1967 that the great Russian virologist Mikhail P. Chumakov and his colleagues formally registered an isolate of the virus from a fatal human case that occurred in Samarkand (in Central Asia, not in the Crimea) in the International Catalogue of Arboviruses Including Certain Other Viruses of Vertebrates (2).  This was the result of a visit, prior to publication of the description of Congo virus, to the second author [JPW] of this article who explained that the isolation had been made in newborn mice rather than in the adult mice the Russians had been using.  The following year the Russians published additional information about their virus (3), but they did not send the virus to the World Arbovirus Reference Center at Yale University, probably because of political constraints. However, and unbeknown to them, in 1956 Ghislain Courtois, a physician working at the Provincial Medical Laboratory in Stanleyville (now Kisangani), Belgian Congo (now Democratic Republic of the Congo), had isolated a virus from the blood of a 13 year-old local African male with fever, headache, nausea, vomiting, backache, generalized joint pains, and photophobia.  Shortly after this virus isolation in his own laboratory, Courtois himself fell ill for three days with high fever and symptoms similar to his young patient.  Courtois isolated a similar virus from his own blood taken on the day of onset of his illness and named it strain V3010.  V3010 was later found in Greece, Portugal, South Africa, Madagascar, the Maghreb, Dubai, Saudi Arabia, Kuwait and Iraq.  Meanwhile, the virus was re-named “Congo virus”, but descriptive information about it was not published until 1967 (4, 5), the year before Chumakov et al. published their findings. Of note, Congo virus was also isolated from a cow in Kenya (4), and from a goat in Nigeria (6). In February 1967, Congo virus strain V3010 was sent to the Rockefeller Foundation Virus Laboratory (RFVL) in New York City and there found by Jordi Casals to be identical to another virus, from Uganda, but to no other named virus. Chumakov later sent his strain to the RFVL, where it was found to be identical to the Congo virus (7, 8).  In 1970, Chumakov published a book in Russian including a chapter on isolations of the virus from ixodid ticks in European Russia.  Also in 1970, British veterinarians in Uganda sent 699 cattle ticks to the East African Virus Research Institute, from which a strain (AMP 10358) of Congo virus was isolated. These findings suggested that ticks could be vectors of the virus to humans and that livestock might constitute at least hosts if not reservoirs of this newly recognized hemorrhagic fever virus.  In May 1973, Greek veterinarians isolated AP 92 virus from ticks feeding on goats in Vergina, northern Greece (9).  Moreover they showed that AP 92 virus clearly reacted in immunodiffusion tests with the same goats’ sera.  In the same study they demonstrated that AP 92 virus reacted in the same way with Russian antisera to Crimean hemorrhagic fever virus and with antisera to Congo virus, provided by Chumakov and Casals, respectively.  Casals’ paradigm was thereby confirmed.  In subsequent years demonstrations of the relatedness of AP 92 and several other Crimean-Congo hemorrhagic fever viruses from Greece and surrounding countries allowed an increasing “One Health approach” to studies of this emerging virus (10). These findings and the dates of their publications created a nomenclatural quandary.  Should the virus be named “Congo virus” because it was isolated first, or should it be named “Crimean hemorrhagic fever virus” because a description of the disease was published first and because it incorporated the name of an important human disease?  Because this situation had both nomenclatural and political implications, the ICTV attempted to find a proper solution to it. Against the principles of scientific nomenclature based on priority of publication, recognizing that Congo virus was the etiologic agent of illnesses other than relatively simple fevers, including hemorrhagic manifestations (4), and because it seemed too late to rename it “Congo hemorrhagic fever virus”, in 1973 the virus finally was re-named “Crimean-Congo hemorrhagic fever virus” (C-CHFV; family Bunyaviridae, genus Nairovirus).  So there are now a number of publications in the literature with “Congo virus” and even “Congo-Crimean hemorrhagic fever virus” in the title.  Of course, this did not satisfy everyone but everyone recognized that life and taxonomists are not perfect and further arguments were settled or at least disregarded.  The virus is now known to be widespread in Africa, and from the Middle East and southern Europe to Asia, due to the preferred dry and sunny biotope of its global vectors, Hyalomma spp. ticks (10, 11). Sin Nombre virus: Hantaviruses (family Bunyaviridae, genus Hantavirus), found essentially world-wide, are known to cause hemorrhagic fever with renal involvement in Asia (Hantaan virus) and, albeit somewhat milder disease, in Europe (Puumala virus).  Hantaviruses are rodent-borne but, while not seriously affecting the rodent host, cause serious, often life-threatening, illnesses in humans.  Prospect Hill hantavirus was recognized in the eastern U.S. but was and is not known to cause human illness.  In the spring of 1993 a then unexplained outbreak of adult respiratory distress syndrome was observed in rural residents of the Four Corners region (where New Mexico, Arizona, Utah, and Colorado are contiguous) of the southwestern U.S.  Antibody to a recognized hantavirus (Puumala virus) was detected in patient sera, suggesting that whatever the etiologic agent, it likely was a hantavirus (12).  It was quickly shown that this disease was caused by a previously unrecognized hantavirus (13). The virus was first named “Muerto Canyon virus” after a nearby Arizona historic site (Spanish: Canyon del Muerto = Canyon of Death) where, in 1863, the U.S. Army killed Native Americans in order to control the land.  That name certainly was unacceptable to Native Americans and to others and so was replaced by “Four Corners virus”.  However, the name Four Corners virus was unacceptable to tourist bureaus and others in the area so was discarded and replaced by the name Sin Nombre (Spanish for “without a name”).  Viruses traditionally are named for the disease they cause, or the place where they were first recognized (or at least a general location, e.g., “eastern equine encephalitis virus”), so this name was not traditional.  However, given the intensity of the epidemiologic and laboratory efforts in the U.S.A. to understand the disease and to prevent it at that time, naming the virus was considered of relatively trivial importance, and the name Sin Nombre virus was accepted by everyone, even if only for expedience. Tick-borne encephalitis virus: Tick-borne encephalitis is the name of a constellation of clinical findings.  It can be caused by any of a number of etiologic agents, including viruses, bacteria, and parasites but is most commonly thought of as being the result of infection with viruses of the family Flaviviridae, genus Flavivirus, although other tick-borne flaviviruses, i.e., Powassan virus, can cause this disease.  For many years these viruses were described as distinct and given distinct names in different locations.  Later, more detailed studies showed that most were redundant descriptions, the data were merged, and the number of names thankfully reduced.  More recently, molecular studies have led to separation of these viruses as subtypes of a single species, Tick-borne encephalitis virus, European subtype, Far Eastern subtype, and Siberian subtype.  This nomenclature (and taxonomy) is far from satisfactory, given that species are non-concrete entities (that is, they do not exist, except as names on lists; 14).  Obviously (to some), there cannot be a real subtype (a virus) of a non-real entity (a taxon).  It is hoped that someday this will be corrected.  Meanwhile, the same confusion of species (taxa) and viruses (the real deal) persists, probably and understandably because a relatively few understand what they are talking about. There are other examples of virus names that are more confusing than helpful.  Viruses named after patients; after phages named for the bacteria from which they were isolated (Staphylococcus phage 44AHJD, for example; how does one teach a student to remember that?); names including the name of the genus to which it belongs (Australian bat lyssavirus and bovine viral diarrhea virus 1 (redundant); viral hemorrhagic septicemia virus Fil3 (viral virus?); and many more.  Veterinarians almost universally call any of the 26 bluetongue viruses “bluetongue virus” when, in fact, “bluetongue” is the name of a disease and Bluetongue virus is the name of the species (taxon) in which these 26 viruses have been placed.  The point to be made is that care should be taken when first naming a virus and inventing a unique abbreviation for it, so that that name and its abbreviation cause the least confusion among those who will be writing and reading about it. Note: Drs. Jan Clement and Charles Calisher are longstanding One Health Supporters http://www.onehealthinitiative.com/supporters.php.  Dr. John (Jack) Woodall is a member of the One Health Initiative team and manager of the OHI website’s ProMED Outbreak Reports page http://www.onehealthinitiative.com/promed.php. References 1. Chumakov, M.P. (1947) A new virus disease - Crimean hemorrhagic fever, News of Medicine.  Virus Diseases. 44:9-11. (In Russian). 2. Karabatsos, N. (ed) (1985). International Catalogue of Arboviruses Including Certain Other Virus of Vertebrates. 3rd ed., San Antonio, Texas. Am. Soc. Trop. Med. Hyg. 3. Chumakov MP, Butenko AM, Shalunova NV, Martianova LI, Smirnova SE, Bashkirtsev IuN, Zavodova TI, Rubin SG, Tkachenko EA, Karmysheva VIa, Reingold VN, Popov GV, and Savinov AP (1968). New data on the viral agent of Crimean   hemorrhagic fever. Vopr Virusol. (in Russian) 13:377. 4. Simpson DI, Knight EM, Courtois G, Williams MC, Weinbren MP, Kibukamusoke JW. (1967) Congo virus: a hitherto undescribed virus occurring in Africa. I. Human isolations--clinical notes. East Afr Med J. (1967) 44:86-92. 5. Woodall JP, Williams MC, Simpson DI. (1967) Congo virus: a hitherto undescribed virus occurring in Africa. II. Identification studies. East Afr Med J. 44:93-8. 6, Causey OR, Kemp GE, Madbouly MH, David-West TS. (1970) Congo virus from domestic livestock, African hedgehog, and arthropods in Nigeria. Am J Trop Med Hyg. 19:846-50. 7. Casals J. (1969) Antigenic similarity between the virus causing Crimean hemorrhagic fever and Congo virus. Proc Soc Exp Biol Med. 131:233-6. 8. Chumakov MP, Smirnova SE, Tkachenko EA. (1970) Relationship between strains of Crimean haemorrhagic fever and Congo viruses. Acta Virol. 14:82-5. 9. Papadopoulos O and Koptopoulos G. (1978) Isolation of Crimean-Congo hemorrhagic fever virus from Rhipicephalus bursa ticks in Greece. Acta Microbio Hellenica. 23:20-8 (in Greek with English summary) 10. Papa A, Dalla V, Papadimitriou E, Kartalis GN, Antoniadis A. (2010) Emergence of Crimean-Congo haemorrhagic fever in Greece. Clin Microbiol Infect. 16:843-7. 11. Bente, DA, Forrester NL, Watts DM, McAuley AJ, Whitehouse CA, Bray M (2013) Crimean-Congo hemorrhagic fever: History, epidemiology, pathogenesis, clinical syndrome and genetic diversity. Antiviral Res. 100:159-89. 12. Centers for Disease Control and Prevention: Update: outbreak of hantavirus infection-southwestern United States, 1993. (1993) Morb Mortal Wkly Rep. 42:441-79. 13. Hjelle B, Jenison S, Torrez-Martinez N, Yamada T, Nolte K, Zumwalt R, MacInnes K, Myers G. (1994) A novel hantavirus associated with an outbreak of fatal respiratory disease in the southwestern United States: evolutionary relationships to known hantaviruses. J Virol. 68:592-6. 14. Van Regenmortel MH. (2003) Viruses are real, virus species are man-made, taxonomic constructions. Arch Virol. 148:2481-8.