Врач с поликлинике осмотрит вас и при подтверждении симптомов простуды отправит на госпитализацию в инфекционный стационар; После госпитализации в больницу у вас возьмут комаровский о коронавирусе в китае видео анализы и отправят биоматериал в ближайший медицинский центр Роспотребнадзора, где с помощью комаровский о коронавирусе в китае видео тест-системы определят наличие или отсутствие нового коронавируса; После получения отрицательных анализов вас комаровский о коронавирусе в китае видео переведут из инфекционного стационара в общий или выпишут домой.
Мэр Москвы Сергей Собянин комаровский о коронавирусе в китае видео ранее заявил , что городские власти уделят «особое внимание» гостиницам и другим местам, комаровский о коронавирусе в китае видео где могут быть туристы из Китая. «При появлении тревожных сигналов туда будут высланы оперативные бригады медиков для проведения сплошного осмотра». Лада Шамардина Читать полностью комаровский о коронавирусе в китае видео Введите ключевые слова. Ничего не найдено :(" FIELD OF THE INVENTION The present invention relates to an attenuated coronavirus comprising a variant replicase gene, which causes the virus to have reduced pathogenicity. The present invention also relates to комаровский о коронавирусе в китае видео the use of such a coronavirus in a vaccine to prevent and/or комаровский о коронавирусе в китае видео treat a disease. BACKGROUND TO THE INVENTION Avian infectious bronchitis virus (IBV), the aetiological agent of infectious bronchitis (IB), is a highly infectious and contagious pathogen of domestic fowl that replicates primarily in the respiratory tract but комаровский о коронавирусе в китае видео also in epithelial cells of the gut, kidney and oviduct. IBV is a member of the Order Nidovirales, Family Coronaviridae, Subfamily Corona virinae and комаровский о коронавирусе в китае видео Genus Gammacoronavirus ; genetically very similar coronaviruses cause disease in turkeys, guinea fowl and pheasants.
Clinical signs of IB include sneezing, tracheal rales, nasal discharge and wheezing. Meat-type birds have reduced weight gain, whilst egg-laying birds lay fewer eggs and produce poor quality eggs.
The respiratory infection predisposes chickens to secondary bacterial infections which can be fatal in chicks. The virus can also cause permanent damage to the oviduct, especially in chicks, leading to reduced egg production and quality; and kidney, sometimes leading to kidney disease which can be fatal. IBV has been reported to be responsible for more economic loss to the poultry industry than any other infectious disease. Although комаровский о коронавирусе в китае видео комаровский о коронавирусе в китае видео live attenuated vaccines and inactivated vaccines are universally used in the control of IBV, the protection gained by use of vaccination can be lost either due to vaccine breakdown or the introduction of a new IBV serotype комаровский о коронавирусе в китае видео that is not related to the vaccine used, posing a risk to комаровский о коронавирусе в китае видео the poultry industry. Further, there is a need in the industry to комаровский о коронавирусе в китае видео develop vaccines which are suitable for use in ovo, in order to improve the efficiency and cost-effectiveness of vaccination programmes.
A major challenge associated with in ovo vaccination is that the virus must be capable of replicating in the presence of maternally-derived antibodies against the virus, without being pathogenic комаровский о коронавирусе в китае видео to the embryo. Current IBV vaccines are derived following multiple passage in embryonated eggs, this results in viruses with reduced pathogenicity for chickens, so that they can be used as live attenuated vaccines. However such viruses almost always show an increased virulence to embryos and therefore cannot be used комаровский о коронавирусе в китае видео for in ova vaccination as they cause reduced hatchability. A 70% reduction in hatchability is seen in some cases.
Attenuation following multiple passage in embryonated eggs also suffers from other disadvantages. It is an empirical method, as комаровский о коронавирусе в китае видео attenuation of the viruses is random and will differ every time the virus is passaged, so passage of the same virus through a different series of eggs for attenuation purposes will lead to a different set of mutations leading to attenuation. There are also efficacy problems associated with the комаровский о коронавирусе в китае видео process: some mutations will affect the replication of the virus and some of the mutations may make the virus too attenuated.
Mutations can also комаровский о коронавирусе в китае видео occur in the S gene which may also affect immunogenicity so that the desired immune response is affected and the potential vaccine may not protect against the required serotype. In addition there are problems associated with reversion to virulence and stability of vaccines. It is important that new and safer vaccines are developed for the control of IBV. Thus there is a need for IBV vaccines which are not associated with these issues, in particular vaccines which may be used for in ovo vaccination. SUMMARY OF ASPECTS OF THE INVENTION The present inventors have used a reverse genetics approach in order to rationally attenuate IBV. This approach is much more controllable than random attenuation following multiple passages in embryonated eggs because the комаровский о коронавирусе в китае видео position of each mutation is known and its effect on the virus, i.e.
Using their reverse genetics approach, the present inventors have identified various комаровский о коронавирусе в китае видео mutations which cause the virus to have reduced levels of pathogenicity. The levels of pathogenicity may be reduced such that when the virus is administered to an embryonated egg, it is capable of replicating without being комаровский о коронавирусе в китае видео pathogenic to the embryo. Such viruses may be suitable for in ovo vaccination, which is a significant advantage and has improvement over attenuated IBV vaccines комаровский о коронавирусе в китае видео produced following multiple passage in embryonated eggs. Thus in a first aspect, the present invention provides a live, attenuated coronavirus comprising a variant replicase комаровский о коронавирусе в китае видео gene encoding polyproteins comprising a mutation in one or more of non-structural protein(s) (nsp)-10, nsp-14, nsp-15 or nsp-16. The variant replicase gene may encode a protein comprising one or more amino acid mutations selected from the list of: Pro to Leu at position 85 of SEQ ID NO: 6, Val to Leu at position 393 of SEQ ID NO: 7; Leu to Ile at position 183 of SEQ ID NO: 8; Val комаровский о коронавирусе в китае видео to Ile at position 209 of SEQ ID NO: 9. The replicase gene may encode a protein comprising the amino acid mutation Pro to Leu at position 85 of SEQ ID NO: 6. The replicase gene may encode a protein comprising the amino acid mutations Val to Leu at position 393 of SEQ ID NO: 7; Leu to Ile at position 183 of SEQ ID NO: 8; and Val to Ile at position 209 of SEQ ID NO: 9. The replicase gene may encodes a комаровский о коронавирусе в китае видео комаровский о коронавирусе в китае видео protein comprising the amino acid mutations Pro to Leu at position 85 of SEQ ID NO: 6; Val to Leu at position 393 of SEQ ID NO:7; Leu to Ile at position 183 of SEQ ID NO:8; and Val to Ile at position 209 of SEQ ID NO: 9. The replicase gene may comprise one or more nucleotide substitutions комаровский о коронавирусе в китае видео selected from the list of: C to T at nucleotide position 12137; G to C at nucleotide position 18114; T to A at nucleotide position 19047; and G to A at nucleotide position 20139; compared to the sequence shown as SEQ ID NO: 1. The coronavirus may be an infectious bronchitis virus (IBV). The coronavirus may comprise an S protein at least part of which is from an IBV serotype other than M41. For example, the S1 subunit or the entire S protein may be from an IBV serotype other than M41. The coronavirus according to the first aspect of the invention has reduced pathogenicity compared to a coronavirus expressing a corresponding wild-type replicase, such that when the virus is administered to комаровский о коронавирусе в китае видео an embryonated egg, it is capable of replicating without being pathogenic to the embryo.
In a second aspect, the present invention provides a variant replicase комаровский о коронавирусе в китае видео gene as defined in connection with the first aspect of the invention. In комаровский о коронавирусе в китае видео a third aspect, the present invention provides a protein encoded by комаровский о коронавирусе в китае видео a variant coronavirus replicase gene according to the second aspect of the invention.
