veterinaryВетеринария сегодняVeterinary Science Today2304-196X2658-6959"Veinard"10.29326/2304-196X-2023-12-1-6-12veterinary-703Research ArticleБИОТЕХНОЛОГИЯBIOTECHNOLOGYСовременные подходы к созданию безопасных и эффективных генно-инженерных антирабических вакцин для животныхModern approaches to production of safe and effective genetically modified rabies vaccines for animalshttps://orcid.org/0000-0002-4682-6559ДоронинМ. И.DoroninM. I.

Доронин Максим Игоревич, кандидат биологических наук, заведующий сектором лаборатории профилактики ящура

г. Владимир

Maksim I. Doronin, Candidate of Science (Biology), Head of Sector, Laboratory for FMD Prevention

Vladimir

doronin@arriah.ruhttps://orcid.org/0000-0002-5982-8393МазлумА.MazloumA.

Мазлум Али, кандидат биологических наук, старший научный  сотрудник референтной лаборатории по африканской чуме свиней

г. Владимир

Ali Mazloum, Candidate of Science (Biology), Senior Researcher, Laboratory for African Swine Fever

Vladimir

mazlum@arriah.ruhttps://orcid.org/0000-0003-1718-1955МихалишинД. В.MikhalishinD. V.

Михалишин Дмитрий Валерьевич, доктор ветеринарных наук, заведующий лабораторией профилактики ящура

г. Владимир

Dmitry V. Mikhalishin, Doctor of Science (Veterinary Medicine), Head of Laboratory for FMD Prevention

Vladimir

mihalishin_dv@arriah.ruhttps://orcid.org/0000-0003-0126-9653МитрофановаМ. Н.MitrofanovaM. N.

Митрофанова Мария Николаевна, кандидат ветеринарных наук, младший научный сотрудник информационно-аналитического центра

г. Владимир

Maria N. Mitrofanova, Candidate of Science (Veterinary Medicine), Junior Researcher, Information and Analysis Centre

Vladimir

mitrofanova@arriah.ruhttps://orcid.org/0000-0001-5326-2440СухарьковА. Ю.SukharkovA. Yu.

Сухарьков Андрей Юрьевич, кандидат биологических наук,  заведующий референтной лабораторией по бешенству и BSE 

г. Владимир

Andrey Yu. Sukharkov, Candidate of Science (Biology), Head of  Reference Laboratory for  Rabies and BSE

Vladimir

suharkov@arriah.ruhttps://orcid.org/0000-0001-7114-6267КиселеваВ. В.KiselevaV. V.

Киселева Валерия Владимировна, ведущий биолог лаборатории по бешенству и BSE

г. Владимир

Valeriya V. Kiseleva, Leading Biologist, Reference Laboratory for Rabies and BSE

Vladimir

kiseleva_vv@arriah.ruhttps://orcid.org/0000-0001-5982-3675СпрыгинА. В.SpryginA. V.

Спрыгин Александр Владимирович, доктор биологических наук, старший научный сотрудник референтной лаборатории болезней крупного рогатого скота

г. Владимир

Alexander V.  Sprygin, Doctor of  Science (Biology), Senior Researcher, Reference Laboratory for  Bovine Diseases

Vladimir

sprygin@arriah.ruФГБУ «Федеральный центр охраны здоровья животных» (ФГБУ «ВНИИЗЖ»)РоссияFGBI “Federal Centre for Animal Health” (FGBI “ARRIAH”)Russian Federation202323032023121612Copyright © Доронин М.И., Мазлум А., Михалишин Д.В., Митрофанова М.Н., Сухарьков А.Ю., Киселева В.В., Спрыгин А.В., 20232023Доронин М.И., Мазлум А., Михалишин Д.В., Митрофанова М.Н., Сухарьков А.Ю., Киселева В.В., Спрыгин А.В.Doronin M.I., Mazloum A., Mikhalishin D.V., Mitrofanova M.N., Sukharkov A.Y., Kiseleva V.V., Sprygin A.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://veterinary.arriah.ru/jour/article/view/703

Бешенство является одним из опасных зоонозов, который вызывает поражение центральной нервной системы, приводит к энцефаломиелитам, параличам с неизбежным летальным исходом. Заболевание наносит значительный экономический ущерб, который связан с гибелью животных, ликвидацией последствий вспышек болезни, введением строгих ограничений, налагаемых на внутреннюю и международную торговлю продукцией животноводства, проведением профилактических и карантинных мероприятий, осуществлением лабораторных исследований. Для борьбы с бешенством Всемирная организация здравоохранения животных рекомендует вакцинопрофилактику. Для глобальной профилактики и борьбы с этим заболеванием производимого количества доступных высококачественных вакцин недостаточно. Стабильные аттенуированные производственные штаммы вируса бешенства с широкой перекрестной активностью против различных вариантов возбудителя являются идеальными кандидатами для создания надежных, безопасных и эффективных препаратов. На сегодняшний день применен ряд подходов для снижения вирулентности вируса и повышения безопасности антирабических вакцин. Большую популярность имеют методы обратной генетики, которые представляют собой новые подходы к исследованию функции конкретного гена путем анализа фенотипических эффектов за счет непосредственного манипулирования последовательностями нуклеотидов. Данная группа методов произвела революцию в молекулярной биологии, стала мощным инструментом для изучения генетики РНК-содержащих вирусов и широко используется в исследованиях возбудителя бешенства. Применение методов обратной генетики позволило проводить модификации производственных штаммов вируса бешенства для использования при изготовлении современных генно-инженерных антирабических препаратов, вызывающих стойкий и длительный иммунитет. В представленном обзоре кратко изложены общие подходы к разработке вирусных векторов с целью создания генно-инженерных вакцин против бешенства.

Rabies is a dangerous zoonoticdisease that affects the central nervous system, causes encephalomyelitis and paralyses and Is almost invariably fatal. The disease causes significant economic losses associated with the death of animals, outbreak consequences, strict restrictions on domestic and international trade in livestock products, preventive and quarantine measures, laboratory tests. The World Organization for Animal Health recommends vaccination to control rabies. Taking into account that there is a lack of affordable high-quality vaccines to globally prevent and control the disease, stable, attenuated production strains of rabies virus with broad cross-activity against various variants of the pathogen shall be considered as ideal candidates to produce high-quality, safe and effective vaccines. Currently, someapproachesareappliedtoreducethevirusvirulenceandimprovesafetyof rabies vaccines. Reverse genetics is very popular now. It provides new approaches to study functions of a specific gene by analyzing phenotypic effects after direct manipulations with nucleotide sequences. The methods of reverse genetics have revolutionized molecular biology and have become apowerful tool to study genetics of RNA viruses. These methods are widely used to study rabies virus. The use of reverse genetics has made it possible to modify rabies virus production strains for manufacture of modern genetically modified rabies vaccines that induce a persistent and long-term immunity. The review briefly covers general approaches to development of viral vectors with the purpose to create genetically modified rabies vaccines.

обзорвирус бешенствагеныгенно-инженерные антирабические вакциныметоды обратной генетикиreviewrabies virusgenesgenetically modified rabies vaccinesmethods of reverse geneticsРабота выполнена в рамках исследовательской программы «Создание комплекса средств защиты против экономически и социально значимых болезней животных на основе отобранных методами геномного секвенирования производственных штаммов микроорганизмов», осуществляемой при выполнении отдельных мероприятий Федеральной научно-технической программы развития генетических технологий на 2019–2027 годы, проводимых при реализации федерального проекта «Развитие масштабных научных и научно-технологических проектов по приоритетным исследовательским направлениям» национального проекта «Наука и университеты».: The work has been done as part of the research program “Creating protection tools for economically and socially significant animal diseases based on production strains of microorganisms selected by genomic sequencing”, implemented within some measures of the Federal Program for Genetic Technologies Development for 2019–2027, taken under the Federal Project “Development of large-scale scientific and scientific-technological projects in priority research areas” of the national project “Science and Universities”.ReferencesHidaka Y., Lim C. K., Takayama-Ito M., Park C. H., Kimitsuki K., Shiwa N., et al. Segmentation of the rabies virus genome. Virus. Res. 2018; 252: 68–75. DOI: 10.1016/j.virusres.2018.05.017.Hidaka Y., Lim C. K., Takayama-Ito M., Park C. H., Kimitsuki K., Shiwa N., et al. Segmentation of the rabies virus genome. Virus. Res. 2018; 252: 68–75. DOI: 10.1016/j.virusres.2018.05.017.Wu X., Smith T. G., Rupprecht C. E. From brain passage to cell adaptation: the road of human rabies vaccine development. Expert. Rev. Vaccines. 2011; 10 (11): 1597–1608. DOI: 10.1586/erv.11.140.Wu X., Smith T. G., Rupprecht C. E. From brain passage to cell adaptation: the road of human rabies vaccine development. Expert. Rev. Vaccines. 2011; 10 (11): 1597–1608. DOI: 10.1586/erv.11.140.Briggs D. J., Nagarajan T., Rupprecht C. E. Rabies vaccines. In: Rabies: Scientific Basis of the Disease and Its Management. Ed. by A. C. Jackson. 3rd ed. Academic Press; 2013; Chapter 13: 497–526. DOI: 10.1016/B978-0-12- 396547-9.00013-4.Briggs D. J., Nagarajan T., Rupprecht C. E. Rabies vaccines. In: Rabies: Scientific Basis of the Disease and Its Management. Ed. by A. C. Jackson. 3rd ed. Academic Press; 2013; Chapter 13: 497–526. DOI: 10.1016/B978-0-12- 396547-9.00013-4.Evans J. S., Horton D. L., Easton A. J., Fooks A. R., Banyard A. C. Rabies virus vaccines: is there a need for a pan-lyssavirus vaccine? Vaccine. 2012; 30 (52): 7447–7454. DOI: 10.1016/j.vaccine.2012.10.015.Evans J. S., Horton D. L., Easton A. J., Fooks A. R., Banyard A. C. Rabies virus vaccines: is there a need for a pan-lyssavirus vaccine? Vaccine. 2012; 30 (52): 7447–7454. DOI: 10.1016/j.vaccine.2012.10.015.Hicks D. J., Fooks A. R., Johnson N. Developments in rabies vaccines. Clin. Exp. Immunol. 2012; 169 (3): 199–204. DOI: 10.1111/j.1365-2249.2012.04592.x.Hicks D. J., Fooks A. R., Johnson N. Developments in rabies vaccines. Clin. Exp. Immunol. 2012; 169 (3): 199–204. DOI: 10.1111/j.1365-2249.2012.04592.x.Hosokawa-Muto J., Ito N., Yamada K., Shimizu K., Sugiyama M., Minamoto N. Characterization of recombinant rabies virus carrying double glycoprotein genes. Microbiol. Immunol. 2006; 50 (3): 187–196. DOI: 10.1111/ j.1348-0421.2006.tb03785.x.Hosokawa-Muto J., Ito N., Yamada K., Shimizu K., Sugiyama M., Minamoto N. Characterization of recombinant rabies virus carrying double glycoprotein genes. Microbiol. Immunol. 2006; 50 (3): 187–196. DOI: 10.1111/ j.1348-0421.2006.tb03785.x.Nel L. H. Vaccines for lyssaviruses other than rabies. Expert. Rev. Vaccines. 2005; 4 (4): 533–540. DOI: 10.1586/14760584.4.4.533.Nel L. H. Vaccines for lyssaviruses other than rabies. Expert. Rev. Vaccines. 2005; 4 (4): 533–540. DOI: 10.1586/14760584.4.4.533.Rupprecht C. E., Plotkin S. A. Rabies vaccines. In: Vaccines. Ed. by S. A. Plotkin, W. A. Orenstein, P. A. Offit. 6th ed. Elsevier Saunders; 2013: 646– 668. DOI: 10.1016/B978-1-4557-0090-5.00036-7.Rupprecht C. E., Plotkin S. A. Rabies vaccines. In: Vaccines. Ed. by S. A. Plotkin, W. A. Orenstein, P. A. Offit. 6th ed. Elsevier Saunders; 2013: 646– 668. DOI: 10.1016/B978-1-4557-0090-5.00036-7.Schnell M. J., Mebatsion T., Conzelmann K. K. Infectious rabies viruses from cloned cDNA. EMBO J. 1994; 13 (18): 4195–4203. DOI: 10.1002/j.1460- 2075.1994.tb06739.x.Schnell M. J., Mebatsion T., Conzelmann K. K. Infectious rabies viruses from cloned cDNA. EMBO J. 1994; 13 (18): 4195–4203. DOI: 10.1002/j.1460- 2075.1994.tb06739.x.Yin J., Wang X., Mao R., Zhang Z., Gao X., Luo Y., et al. Research advances on the interactions between rabies virus structural proteins and host target cells: accrued knowledge from the application of reverse genetics systems. Viruses. 2021; 13 (11):2288. DOI: 10.3390/v13112288.Yin J., Wang X., Mao R., Zhang Z., Gao X., Luo Y., et al. Research advances on the interactions between rabies virus structural proteins and host target cells: accrued knowledge from the application of reverse genetics systems. Viruses. 2021; 13 (11):2288. DOI: 10.3390/v13112288.Conzelmann K. K. Reverse Genetics of Mononegavirales: The Rabies Virus Paradigm. In: Sendai Virus Vector. Ed. by Y. Nagai. Tokyo: Springer; 2013: 1–20. DOI: 10.1007/978-4-431-54556-9_1.Conzelmann K. K. Reverse Genetics of Mononegavirales: The Rabies Virus Paradigm. In: Sendai Virus Vector. Ed. by Y. Nagai. Tokyo: Springer; 2013: 1–20. DOI: 10.1007/978-4-431-54556-9_1.Huang Y., Tang Q., Nadin-Davis S. A., Zhang S., Hooper C. D., Ming P., et al. Development of a reverse genetics system for a human rabies virus vaccine strain employed in China. Virus. Res. 2010; 149 (1): 28–35. DOI: 10.1016/j.virusres.2009.12.009.Huang Y., Tang Q., Nadin-Davis S. A., Zhang S., Hooper C. D., Ming P., et al. Development of a reverse genetics system for a human rabies virus vaccine strain employed in China. Virus. Res. 2010; 149 (1): 28–35. DOI: 10.1016/j.virusres.2009.12.009.Larsen D. D., Wickersham I. R., Callaway E. M. Retrograde tracing with recombinant rabies virus reveals correlations between projection targets and dendritic architecture in layer 5 of mouse barrel cortex. Front. Neural Circuits. 2008; 1:5. DOI: 10.3389/neuro.04.005.2007.Larsen D. D., Wickersham I. R., Callaway E. M. Retrograde tracing with recombinant rabies virus reveals correlations between projection targets and dendritic architecture in layer 5 of mouse barrel cortex. Front. Neural Circuits. 2008; 1:5. DOI: 10.3389/neuro.04.005.2007.Conzelmann K. K., Cox J. H., Schneider L. G., Thiel H. J. Molecular cloning and complete nucleotide sequence of the attenuated rabies virus SAD B19. Virology. 1990; 175 (2): 485–499. DOI: 10.1016/0042-6822(90)90433-r.Conzelmann K. K., Cox J. H., Schneider L. G., Thiel H. J. Molecular cloning and complete nucleotide sequence of the attenuated rabies virus SAD B19. Virology. 1990; 175 (2): 485–499. DOI: 10.1016/0042-6822(90)90433-r.Finke S., Conzelmann K. K. Recombinant rhabdoviruses: vectors for vaccine development and gene therapy. Curr. Top. Microbiol. Immunol. 2005; 292: 165–200. DOI: 10.1007/3-540-27485-5_8.Finke S., Conzelmann K. K. Recombinant rhabdoviruses: vectors for vaccine development and gene therapy. Curr. Top. Microbiol. Immunol. 2005; 292: 165–200. DOI: 10.1007/3-540-27485-5_8.Finke S., Mueller-Waldeck R., Conzelmann K. K. Rabies virus matrix protein regulates the balance of virus transcription and replication. J. Gen. Virol. 2003; 84: 1613–1621. DOI: 10.1099/vir.0.19128-0. PMID: 12771432.Finke S., Mueller-Waldeck R., Conzelmann K. K. Rabies virus matrix protein regulates the balance of virus transcription and replication. J. Gen. Virol. 2003; 84: 1613–1621. DOI: 10.1099/vir.0.19128-0. PMID: 12771432.Mebatsion T. Extensive attenuation of rabies virus by simultaneously modifying the dynein light chain binding site in the P protein and replacing Arg333 in the G protein. J. Virol. 2001; 75 (23): 11496–11502. DOI: 10.1128/ JVI.75.23.11496-11502.2001.Mebatsion T. Extensive attenuation of rabies virus by simultaneously modifying the dynein light chain binding site in the P protein and replacing Arg333 in the G protein. J. Virol. 2001; 75 (23): 11496–11502. DOI: 10.1128/ JVI.75.23.11496-11502.2001.Morimoto K., Shoji Y., Inoue S. Characterization of P gene-deficient rabies virus: propagation, pathogenicity and antigenicity. Virus. Res. 2005; 111 (1): 61–67. DOI: 10.1016/j.virusres.2005.03.011.Morimoto K., Shoji Y., Inoue S. Characterization of P gene-deficient rabies virus: propagation, pathogenicity and antigenicity. Virus. Res. 2005; 111 (1): 61–67. DOI: 10.1016/j.virusres.2005.03.011.Wang Z. W., Sarmento L., Wang Y., Li X. Q., Dhingra V., Tseggai T., et al. Attenuated rabies virus activates, while pathogenic rabies virus evades, the host innate immune responses in the central nervous system. J. Virol. 2005; 79 (19): 12554–12565. DOI: 10.1128/JVI.79.19.12554-12565.2005.Wang Z. W., Sarmento L., Wang Y., Li X. Q., Dhingra V., Tseggai T., et al. Attenuated rabies virus activates, while pathogenic rabies virus evades, the host innate immune responses in the central nervous system. J. Virol. 2005; 79 (19): 12554–12565. DOI: 10.1128/JVI.79.19.12554-12565.2005.Walker P. J., Dietzgen R. G., Joubert D. A., Blasdell K. R. Rhabdovirus accessory genes. Virus. Res. 2011; 162 (1–2): 110–125. DOI: 10.1016/j.virusres.2011.09.004.Walker P. J., Dietzgen R. G., Joubert D. A., Blasdell K. R. Rhabdovirus accessory genes. Virus. Res. 2011; 162 (1–2): 110–125. DOI: 10.1016/j.virusres.2011.09.004.Faber M., Faber M. L., Papaneri A., Bette M., Weihe E., Dietzschold B., Schnell M. J. A single amino acid change in rabies virus glycoprotein increases virus spread and enhances virus pathogenicity. J. Virol. 2005; 79 (22): 14141–14148. DOI: 10.1128/JVI.79.22.14141-14148.2005.Faber M., Faber M. L., Papaneri A., Bette M., Weihe E., Dietzschold B., Schnell M. J. A single amino acid change in rabies virus glycoprotein increases virus spread and enhances virus pathogenicity. J. Virol. 2005; 79 (22): 14141–14148. DOI: 10.1128/JVI.79.22.14141-14148.2005.Etessami R., Conzelmann K. K., Fadai-Ghotbi B., Natelson B., Tsiang H., Ceccaldi P. E. Spread and pathogenic characteristics of a G-deficient rabies virus recombinant: an in vitro and in vivo study. J. Gen. Virol. 2000; 81: 2147–2153. DOI: 10.1099/0022-1317-81-9-2147.Etessami R., Conzelmann K. K., Fadai-Ghotbi B., Natelson B., Tsiang H., Ceccaldi P. E. Spread and pathogenic characteristics of a G-deficient rabies virus recombinant: an in vitro and in vivo study. J. Gen. Virol. 2000; 81: 2147–2153. DOI: 10.1099/0022-1317-81-9-2147.Yan X., Prosniak M., Curtis M. T., Weiss M. L., Faber M., Dietzschold B., Fu Z. F. Silver-haired bat rabies virus variant does not induce apoptosis in the brain of experimentally infected mice. J. Neurovirol. 2001; 7 (6): 518–527. DOI: 10.1080/135502801753248105.Yan X., Prosniak M., Curtis M. T., Weiss M. L., Faber M., Dietzschold B., Fu Z. F. Silver-haired bat rabies virus variant does not induce apoptosis in the brain of experimentally infected mice. J. Neurovirol. 2001; 7 (6): 518–527. DOI: 10.1080/135502801753248105.Zhang G., Wang H., Mahmood F., Fu Z. F. Rabies virus glycoprotein is an important determinant for the induction of innate immune responses and the pathogenic mechanisms. Vet. Microbiol. 2013; 162 (2–4): 601–613. DOI: 10.1016/j.vetmic.2012.11.031.Zhang G., Wang H., Mahmood F., Fu Z. F. Rabies virus glycoprotein is an important determinant for the induction of innate immune responses and the pathogenic mechanisms. Vet. Microbiol. 2013; 162 (2–4): 601–613. DOI: 10.1016/j.vetmic.2012.11.031.Tao L., Ge J., Wang X., Wen Z., Zhai H., Hua T., et al. Generation of a recombinant rabies Flury LEP virus carrying an additional G gene creates an improved seed virus for inactivated vaccine production. Virol. J. 2011; 8:454. DOI: 10.1186/1743-422X-8-454.Tao L., Ge J., Wang X., Wen Z., Zhai H., Hua T., et al. Generation of a recombinant rabies Flury LEP virus carrying an additional G gene creates an improved seed virus for inactivated vaccine production. Virol. J. 2011; 8:454. DOI: 10.1186/1743-422X-8-454.Tan Y., Liang H., Chen A., Guo X. Coexpression of double or triple copies of the rabies virus glycoprotein gene using a ‘self-cleaving’ 2A peptide-based replication-defective human adenovirus serotype 5 vector. Biologicals. 2010; 38 (5): 586–593. DOI: 10.1016/j.biologicals.2010.06.001.Tan Y., Liang H., Chen A., Guo X. Coexpression of double or triple copies of the rabies virus glycoprotein gene using a ‘self-cleaving’ 2A peptide-based replication-defective human adenovirus serotype 5 vector. Biologicals. 2010; 38 (5): 586–593. DOI: 10.1016/j.biologicals.2010.06.001.Ito Y., Ito N., Saito S., Masatani T., Nakagawa K., Atoji Y., Sugiyama M. Amino acid substitutions at positions 242, 255 and 268 in rabies virus glycoprotein affect spread of viral infection. Microbiol. Immunol. 2010; 54 (2): 89–97. DOI: 10.1111/j.1348-0421.2009.00192.x.Ito Y., Ito N., Saito S., Masatani T., Nakagawa K., Atoji Y., Sugiyama M. Amino acid substitutions at positions 242, 255 and 268 in rabies virus glycoprotein affect spread of viral infection. Microbiol. Immunol. 2010; 54 (2): 89–97. DOI: 10.1111/j.1348-0421.2009.00192.x.Zandi F., Khalaj V., Goshadrou F., Meyfour A., Gholami A., Enayati S., et al. Rabies virus matrix protein targets host actin cytoskeleton: a protein-protein interaction analysis. Pathog. Dis. 2021; 79 (1):ftaa075. DOI: 10.1093/femspd/ftaa075.Zandi F., Khalaj V., Goshadrou F., Meyfour A., Gholami A., Enayati S., et al. Rabies virus matrix protein targets host actin cytoskeleton: a protein-protein interaction analysis. Pathog. Dis. 2021; 79 (1):ftaa075. DOI: 10.1093/femspd/ftaa075.Mebatsion T., Konig M., Conzelmann K. K. Budding of rabies virus particles in the absence of the spike glycoprotein. Cell. 1996; 84 (6): 941–951. DOI: 10.1016/s0092-8674(00)81072-7.Mebatsion T., Konig M., Conzelmann K. K. Budding of rabies virus particles in the absence of the spike glycoprotein. Cell. 1996; 84 (6): 941–951. DOI: 10.1016/s0092-8674(00)81072-7.Wirblich C., Tan G. S., Papaneri A., Godlewski P. J., Orenstein J. M., Harty R. N., Schnell M. J. PPEY motif within the rabies virus (RV) matrix protein is essential for efficient virion release and RV pathogenicity. J. Virol. 2008; 82 (19): 9730–9738. DOI: 10.1128/JVI.00889-08.Wirblich C., Tan G. S., Papaneri A., Godlewski P. J., Orenstein J. M., Harty R. N., Schnell M. J. PPEY motif within the rabies virus (RV) matrix protein is essential for efficient virion release and RV pathogenicity. J. Virol. 2008; 82 (19): 9730–9738. DOI: 10.1128/JVI.00889-08.Schnell M. J., McGettigan J. P., Wirblich C., Papaneri A. The cell biology of rabies virus: using stealth to reach the brain. Nat. Rev. Microbiol. 2010; 8 (1): 51–61. DOI: 10.1038/nrmicro2260.Schnell M. J., McGettigan J. P., Wirblich C., Papaneri A. The cell biology of rabies virus: using stealth to reach the brain. Nat. Rev. Microbiol. 2010; 8 (1): 51–61. DOI: 10.1038/nrmicro2260.Schnell M. J., Tan G. S., Dietzschold B. The application of reverse genetics technology in the study of rabies virus (RV) pathogenesis and for the development of novel RV vaccines. J. Neurovirol. 2005; 11 (1): 76–81. DOI: 10.1080/13550280590900436.Schnell M. J., Tan G. S., Dietzschold B. The application of reverse genetics technology in the study of rabies virus (RV) pathogenesis and for the development of novel RV vaccines. J. Neurovirol. 2005; 11 (1): 76–81. DOI: 10.1080/13550280590900436.Jacob Y., Badrane H., Ceccaldi P. E., Tordo N. Cytoplasmic dynein LC8 interacts with lyssavirus phosphoprotein. J. Virol. 2000; 74 (21): 10217–10222. DOI: 10.1128/jvi.74.21.10217-10222.2000.Jacob Y., Badrane H., Ceccaldi P. E., Tordo N. Cytoplasmic dynein LC8 interacts with lyssavirus phosphoprotein. J. Virol. 2000; 74 (21): 10217–10222. DOI: 10.1128/jvi.74.21.10217-10222.2000.Ceccaldi P. E., Fayet J., Conzelmann K. K., Tsiang H. Infection characteristics of rabies virus variants with deletion or insertion in the pseudogene sequence. J.Neurovirol. 1998; 4 (1): 115–119. DOI: 10.3109/13550289809113489.Ceccaldi P. E., Fayet J., Conzelmann K. K., Tsiang H. Infection characteristics of rabies virus variants with deletion or insertion in the pseudogene sequence. J.Neurovirol. 1998; 4 (1): 115–119. DOI: 10.3109/13550289809113489.Inoue K., Shoji Y., Kurane I., Iijima T., Sakai T., Morimoto K. An improved method for recovering rabies virus from cloned cDNA. J. Virol. Methods. 2003; 107 (2): 229–236. DOI: 10.1016/s0166-0934(02)00249-5.Inoue K., Shoji Y., Kurane I., Iijima T., Sakai T., Morimoto K. An improved method for recovering rabies virus from cloned cDNA. J. Virol. Methods. 2003; 107 (2): 229–236. DOI: 10.1016/s0166-0934(02)00249-5.Le Mercier P., Jacob Y., Tanner K., Tordo N. A novel expression cassette of lyssavirus shows that the distantly related Mokola virus can rescue a defective rabies virus genome. J. Virol. 2002; 76 (4): 2024–2027. DOI: 10.1128/jvi.76.4.2024-2027.2002.Le Mercier P., Jacob Y., Tanner K., Tordo N. A novel expression cassette of lyssavirus shows that the distantly related Mokola virus can rescue a defective rabies virus genome. J. Virol. 2002; 76 (4): 2024–2027. DOI: 10.1128/jvi.76.4.2024-2027.2002.Buchholz U. J., Finke S., Conzelmann K. K. Generation of bovine respiratory syncytial virus (BRSV) from cDNA: BRSV NS2 is not essential for virus replication in tissue culture, and the human RSV leader region acts as a functional BRSV genome promoter. J. Virol. 1999; 73 (1): 251–259. DOI: 10.1128/JVI.73.1.251-259.1999.Buchholz U. J., Finke S., Conzelmann K. K. Generation of bovine respiratory syncytial virus (BRSV) from cDNA: BRSV NS2 is not essential for virus replication in tissue culture, and the human RSV leader region acts as a functional BRSV genome promoter. J. Virol. 1999; 73 (1): 251–259. DOI: 10.1128/JVI.73.1.251-259.1999.Wenqiang J., Yin X., Lan X., Li X., Liu J. Development of a reverse genetics system for the aG strain of rabies virus in China. Arch. Virol. 2014; 159 (5): 1033–1038. DOI: 10.1007/s00705-013-1919-9.Wenqiang J., Yin X., Lan X., Li X., Liu J. Development of a reverse genetics system for the aG strain of rabies virus in China. Arch. Virol. 2014; 159 (5): 1033–1038. DOI: 10.1007/s00705-013-1919-9.Wall N. R., Wickersham I. R., Cetin A., De La Parra M., Callaway E. M. Monosynaptic circuit tracing in vivo through Cre-dependent targeting and complementation of modified rabies virus. Proc. Natl. Acad. Sci. USA. 2010; 107 (50): 21848–21853. DOI: 10.1073/pnas.1011756107.Wall N. R., Wickersham I. R., Cetin A., De La Parra M., Callaway E. M. Monosynaptic circuit tracing in vivo through Cre-dependent targeting and complementation of modified rabies virus. Proc. Natl. Acad. Sci. USA. 2010; 107 (50): 21848–21853. DOI: 10.1073/pnas.1011756107.Wickersham I. R., Finke S., Conzelmann K. K., Callaway E. M. Retrograde neuronal tracing with a deletion-mutant rabies virus. Nat. Methods. 2007; 4 (1): 47–49. DOI: 10.1038/nmeth999.Wickersham I. R., Finke S., Conzelmann K. K., Callaway E. M. Retrograde neuronal tracing with a deletion-mutant rabies virus. Nat. Methods. 2007; 4 (1): 47–49. DOI: 10.1038/nmeth999.Wickersham I. R., Sullivan H. A., Seung H. S. Production of glycoprotein-deleted rabies viruses for monosynaptic tracing and high-level gene expression in neurons. Nat. Protoc. 2010; 5 (3): 595–606. DOI: 10.1038/ nprot.2009.248.Wickersham I. R., Sullivan H. A., Seung H. S. Production of glycoprotein-deleted rabies viruses for monosynaptic tracing and high-level gene expression in neurons. Nat. Protoc. 2010; 5 (3): 595–606. DOI: 10.1038/ nprot.2009.248.

The authors declare that there are no conflicts of interest present.