title: Increased pathogenicity of rabies virus due to modification of a non-coding region.
abstract: Sub-passaging of QS-05, a street rabies virus (RABV) isolate, in non-neuronal cells resulted in a virus with higher pathogenicity, QS-BHK-P7. Four full-length cDNA plasmids were constructed and the corresponding recombinant viruses were recovered: rQS-05, rQS-BHK-P7 and rQS05-2475G/rQS-BHK-P7-2475A (made by switching of intergenic P-M between these two backbones). rQS-BHK-P7-2475 A virus had eight instead of seven adenosines in its poly(A) sequence. Interestingly, mutant viruses with 6 or 8 adenosines infected more neuroblastoma cells than their parental ones. Mice that were infected intracerebrally and intramuscularly with rQS05-2475G and rQS-BHK-P7 exhibited highest mortality. However, mice infected with rQS-BHK-P7-2475AA had the shortest survival time. This study demonstrates that modifications in the non-coding region may play a role in determining the virulence of RABV.
authors: Faculty of Medicine, WHO Collaborating Centre for Research and Training on Viral Zoonoses, King Chulalongkorn Memorial Hospital, Chulalongkorn University, The Thai Red Cross Society, Bangkok, 10330, Thailand. phatthamon@gmail.com.
authors: Phatthamon
authors: http://orcid.org/0000-0003-1154-759X
authors: P
authors: Virojanapirom
authors: Department of Microbiology, School of Medicine, Oita University, Yufu, Oita, Japan.
authors: Kentaro
authors: K
authors: Yamada
authors: Queen Saovabha Memorial Institute, Thai Red Cross Society, Bangkok, Thailand.
authors: Pakamatz
authors: P
authors: Khawplod
authors: Department of Microbiology, School of Medicine, Oita University, Yufu, Oita, Japan.
authors: Akira
authors: A
authors: Nishizono
authors: Faculty of Medicine, WHO Collaborating Centre for Research and Training on Viral Zoonoses, King Chulalongkorn Memorial Hospital, Chulalongkorn University, The Thai Red Cross Society, Bangkok, 10330, Thailand.
authors: Thiravat
authors: T
authors: Hemachudha
mesh_terms: D000818:Animals; D002460:Cell Line; D005260:Female; D007273:Injections, Intramuscular; D008813:Mice, Inbred ICR; D009474:Neurons / Q000821:virology; D012333:RNA, Messenger / Q000235:genetics*; D022661:RNA, Untranslated / Q000235:genetics*; D012367:RNA, Viral / Q000235:genetics*; D011818:Rabies / Q000473:pathology; D011820:Rabies virus / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity*; D016019:Survival Analysis; D013997:Time Factors; D014774:Virulence; D014776:Virus Cultivation
chemical_list: D012333:RNA, Messenger; D022661:RNA, Untranslated; D012367:RNA, Viral
keywords: Non-coding region; Polyadenylation; Rabies virus; Reverse genetics; Virulence