© Borgis - Postępy Nauk Medycznych 11/2014, s. 766-769
*Tadeusz Wojciech Łapiński
Nowoodkryte koronawirusy
Novel coronaviruses
Department of Infectious Diseases and Hepatology, Medical University, Białystok
Head of Department: prof. Robert Flisiak, MD, PhD
Streszczenie
Obecnie znanych jest sześć grup koronawirusów odpowiedzialnych za choroby występujące wśród ludzi. Koronawirusy 229E, OC43, NL63, HKU1-NH są częstą przyczyną zakażeń górnych dróg oddechowych wśród ludzi. Przebieg tych zakażeń jest zazwyczaj zbliżony do infekcji wirusami grypy. Wirusy te występują na całym świecie, jednak najczęściej w Azji. HVCo-SARS oraz HVCo-MERS uznawane są obecnie za najgroźniejsze spośród znanych koronawirusów. Zakażenie HVCo-SARS rozpoznano po raz pierwszy w prowincji Guangdong w południowo-wschodnich Chinach w 2002 roku. Przebieg choroby był gwałtowny, dominowały objawy niewydolności oddechowej i gorączka. Szybkie działania służb epidemiologicznych zapobiegło rozprzestrzenianiu się wirusa i spowodowało wygaszenie rozpoczynającej się epidemii. W roku 2012 wyizolowano nowego koronawirusa określanego nazwą HVCo-MERS (ang. Middle East Respiratory Virus). Dane epidemiologiczne wskazują, że miejscem, z którego aktualnie rozprzestrzenia się epidemia, jest Arabia Saudyjska. Prawdopodobnym źródłem zakażenia są niektóre gatunki nietoperzy i udomowionych zwierząt, głównie wielbłądów. Przebieg kliniczny zakażenia jest zbliżony do zakażenia HVCo-SARS, ale dodatkowo współistnieją objawy uszkodzenia nerek. Śmiertelność wynosi około 50%. Wirus trafił już do Europy. Pierwsze przypadki zachorowań zanotowano wśród osób powracających ze Zjednoczonych Emiratów Arabskich do Francji, Wielkiej Brytanii i Niemiec. Zarówno WHO, jak i ECDC z wielkim niepokojem monitorują szybkie rozprzestrzenianie się HVCo-MERS.
Summary
Currently, there are six known groups of coronaviruses responsible for the disease occurring in humans. The coronaviruses 229E, OC43, NL63, HKU1-NH are a common cause of upper respiratory tract infections in humans. The course of infection is generally similar to influenza virus infection. These viruses are distributed around the world, but most commonly in Asia. HVCo-SARS and HVCo-MERS are currently regarded as the most dangerous of the known coronaviruses. HVCo-SARS infection was diagnosed for the first time in the province of Guangdong in the south-eastern China in 2002. The disease was the rapid, dominated by symptoms of respiratory failure and fever. Quick actions of epidemiologists prevented the spread of the virus and resulted in extinction beginning of the epidemic. In 2012, a new coronavirus was isolated know as a HVCo-MERS (Middle East Respiratory Virus). Epidemiological data indicate that the place of current spread of epidemic is Saudi Arabia. The probable source of infection are some species of bats and domesticated animals, mainly camels. The clinical course of infection is similar to that of the HVCo-SARS infection with coexisting symptoms of kidney damage. The mortality is about 50%. The virus is detected in Europe. The first reported cases of infection are among persons returning from the United Arab Emirates to France, Britain and Germany. Both the WHO and ECDC with great concern monitor the rapid spread of HVCo-MERS.
Introduction
Coronaviruses belong to Coronaviridae subfamily. These are large spheric RNA viruses with an envelope with bulbous protein projections resembling the colar corona. The genome is a single RNA strand of helical symmetry. Coronaviruses are divided into four kinds depending on the structure of their protein sequence. HCoV-229E and HCoV-NL63 are classified to Alphacoronaviruses while HCoV-OC43, HCoV-HKU1, HCoV-SARS and HCoV-MERS – to Betacoronaviruses. Pathogenic viruses of Gammacoronaviruses and Deltacoronaviruses have not been described yet (1). Coronaviruses can be found world-wide. They show tropism to epithelial cells of the air passages, particularly ciliary epithelial cells. Viral RNA replicates in the cellular nucleus, which it leaves and binds to a capsule part in the cytoplasm. Coronaviruses are cytotoxic to the cells they use as the replication site. They are frequent factor of upper respiratory and alimentary tracts infections. Mammals and birds are susceptible to the infections caused by these viruses. Coronaviruses are responsible for enteritis in pigs, cattle, and dogs and for peritonitis in cats (mainly coronavirus FIP).
Only two pathogenic for humans viruses (HCoV-229E and HCoV-OC43) have been known up to 2003. They were responsible for upper respiratory tract infections. At present, HCoV-NL63 and HCoV-HKU1, also responsible for upper and lower respiratory tract infections, have been described. Coronaviruses 229E, NL63, HKU1 and OC43 are viruses occurring world-wide. Numerous epidemiological data indicate China to be the most probable place of their origin.
Among coronaviruses, there are two specifically dangerous: HCoV-SARS, responsible for severe pneumonia and HCoV-MERS – responsible for pneumonia with coexisting kidney damage. The infection is usually severe with unfavourable prognosis.
Coronaviruses OC43
There are four genotypes of HCoV-OC43 (from A to D). Unlike in case of such viruses as 229E, NL63 or HKU1, the season of the year does not influence the rate of droplet infection. These viruses are responsible for respiratory tract infections which frequently lead to pneumonia. Among patients with upper respiratory tract infections without pneumonia, dominating symptoms are fever, weakness, abdominal pain, rhinitis, and sore throat. Vabret et al., estimating the causes of upper respiratory infections in France, observed HCoV-OC43 infection in 6% of patients (2). The infections with these viruses can be the cause of severe pneumonia, specifically in small children, elderly people, and patients with decreased immunological response, including HIV patients. HCoV-OC43 can infect and multiply in the neurons causing inflammatory conditions and degenerative changes. It seems that these viruses can be responsible for certain undefined central nervous system damage in humans. Animal studies confirmed these viruses to be the cause of encephalitis and paralytic changes depending on viral external protein activity on the glutamate receptors (3). In HcoV-OC43 patients with CNS damage, the beneficial influence of these receptors antagonists was used (4).
It seems coronavirus infections occur more frequently in children than in adults. Dijkman et al. carried out the study in Amsterdam in the group of 1471 children hospitalized due to respiratory tract infections and observed in 14% of children the infection with OC43, HKU1, 229E, and NL63 coronaviruses. HCoV-OC43 infections are the most frequent infections among isolated coronaviruses (5). In the studies, carried out in Brazil by Cabeça et al., coronaviral infections were observed in 88 out of 1137 (7.7%) adult patients hospitalized due to the symptoms of respiratory tract infections. The kind of coronaviruses that are the most frequent cause of infections changes in particular years. The studies, performed by Cabeça et al. in Brazil in 2004-2008, revealed that the coronavirus responsible for infections in 62% of patients was mainly HCoV-229E while in 2008 it was HCoV-NL63 (71%) (6).
Coronaviruses 229E
HCoV-229E is human pathogen with no pathogenic activity to other mammals or birds. They bind to superficial receptors of the cells built with aminopeptidases and metaloproteinases. These receptors occur most frequently on epithelial cells of the intestines, lungs, kidneys and macrophages (7). HCoV-229E infection is manifested by high fever, sore throat, cough, shivering, rhinitis, excessive mucous production in the bronchial tree. Additionally, headaches and myalgia are often observed while vomiting and diarrhoea – rarely. These symptoms are similar to those induced by other coronaviruses, such as OC43, HKU1, and NL63. Among four coronaviruses, responsible for upper respiratory tract infections, HCoV-229E was most frequent in China according to Lu et al. studies (8).
Coronaviruses NL63
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Piśmiennictwo
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