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Evolutionary characteristics of morbilliviruses during serial passages in vitro: Gradual attenuation of virus
Fuxiao Liu1, Xiaodong Wu1, Lin Li1
1OIE Reference Laboratory for Peste des Petits Ruminants, National Research Center for Exotic Animal Diseases, China Animal Health and Epidemiology Center, No. 369 Nanjing Road, Qingdao, Shandong 266032, China.
Abstract:
The genus Morbillivirus is classified into the family Paramyxoviridae, and is composed of 6 members, namely measles virus (MV), rinderpest virus (RPV), peste-des-petits-ruminants virus (PPRV), canine distemper virus (CDV), phocine distemper virus (PDV) and cetacean morbillivirus (CeMV). The MV, RPV, PPRV and CDV have been successfully attenuated through their serial passages in vitro for the production of live vaccines. It has been demonstrated that the morbilliviral virulence in animals was progressively attenuated with their consecutive passages in vitro. However, only a few reports were involved in explanation of an attenuation-related mechanism on them until many years after the establishment of a quasispecies theory. RNA virus quasispecies arise from rapid evolution of viruses with high mutation rate during genomic replication, and play an important role in gradual loss of viral virulence by serial passages. Here, we overviewed the development of live-attenuated vaccine strains against morbilliviruses by consecutive passages in vitro, and further discussed a related mechanism concerning the relationship between virulence attenuation and viral evolution.
Insights
Live-attenuated morbillivirus vaccines are developed through serial in vitro passages, progressively reducing viral virulence. Viral quasispecies, arising from high mutation rates, explain this attenuation mechanism and its link to evolution.
Area of Science:
- Virology
- Vaccinology
- Molecular Biology
Background:
- Morbillivirus, part of the Paramyxoviridae family, includes significant pathogens like measles virus (MV) and canine distemper virus (CDV).
- Live-attenuated vaccines against MV, rinderpest virus (RPV), peste-des-petits-ruminants virus (PPRV), and CDV have been successfully developed via serial in vitro passages.
- Progressive attenuation of morbillivirus virulence correlates with in vitro passaging, but the underlying mechanisms remain underexplored.
Purpose of the Study:
- To review the development of live-attenuated vaccine strains for morbilliviruses.
- To discuss the molecular mechanisms linking viral attenuation and evolution during serial in vitro passages.
- To highlight the role of RNA virus quasispecies in virulence reduction.
Main Methods:
- Literature review on morbillivirus attenuation and vaccine development.
- Analysis of studies investigating the relationship between in vitro passaging and virulence reduction.
- Discussion of the quasispecies theory in the context of morbillivirus evolution.
Main Results:
- Serial in vitro passages lead to progressive attenuation of morbillivirus virulence.
- RNA virus quasispecies, characterized by high mutation rates, are implicated in the gradual loss of virulence.
- The evolution of viral quasispecies during passaging is a key factor in generating attenuated strains.
Conclusions:
- Live-attenuated morbillivirus vaccines are effectively produced through serial in vitro passaging.
- The quasispecies theory provides a framework for understanding the attenuation mechanism.
- Viral evolution, driven by high mutation rates and quasispecies dynamics, is central to developing safer and effective morbillivirus vaccines.
