Episodic adaptive diversification of classical swine fever virus RNA-dependent RNA polymerase NS5B

Li, Yán; Yang, Zexiao

doi:10.1139/cjm-2015-0334

Cited by 4 publications

(1 citation statement)

References 42 publications

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“…[41][42][43] Notably, in classical swine fever virus of the genus Pestivirus, it has been reported that adaptive diversification has occurred on the RdRp NS5B between two major groups, which could be relevant to their virulence diversity. 44 In hepatitis C virus of the genus Hepacivirus, a number of adaptive changes have also taken place on the polymerase NS5B with the split of the predominant subtypes 1a and 1b. 45 Thus, the accumulated results implied that the changes on the NS5 proteins frequently constitute a genetic signature relevant to the biological diversity and (or) large-scale dissemination of the viruses in the family Flaviviridae.…”

Section: Discussionmentioning

confidence: 99%

Adaptive Diversification Between Yellow Fever Virus West African and South American Lineages: A Genome-Wide Study

Yang

2017

The American Society of Tropical Medicine and Hygiene

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Abstract. Yellow fever virus (YFV) has emerged as the causative agent of a vector-borne disease with devastating mortality in the tropics of Africa and the Americas. YFV phylogenies indicate that the isolates collected from West Africa, East and Central Africa, and South America cluster into different lineages and the virus spread into the Americas from Africa. To determine the nature of genetic variation accompanying the intercontinental epidemic, we performed a genome-wide evolutionary study on the West African and South American lineages of YFV. Our results reveal that adaptive genetic diversification has occurred on viral nonstructural protein 5 (NS5), which is crucially required for viral genome replication, in the early epidemic phase of these currently circulating lineages. Furthermore, major amino acid changes relevant to the adaptive diversification generally cluster in different structural regions of NS5 in a lineage-specific manner. These results suggest that YFV has experienced adaptive diversification in the epidemic spread between the continents and shed insights into the genetic determinants of such diversification, which might be beneficial for understanding the emergence and re-emergence of yellow fever as an important global public health issue.

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Section: Discussionmentioning

confidence: 99%

Adaptive Diversification Between Yellow Fever Virus West African and South American Lineages: A Genome-Wide Study

Yang

2017

The American Society of Tropical Medicine and Hygiene

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Crystal Structure of Classical Swine Fever Virus NS5B Reveals a Novel N-Terminal Domain

Soca

et al. 2018

J Virol

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Classical swine fever virus (CSFV) is the cause of classical swine fever (CSF). Nonstructural protein 5B (NS5B) is an RNA-dependent RNA polymerase (RdRp) that is a key enzyme initiating viral RNA replication by a mechanism. It is also an attractive target for the development of anti-CSFV drugs. To gain a better understanding of the mechanism of CSFV RNA synthesis, here, we solved the first crystal structure of CSFV NS5B. Our studies show that the CSFV NS5B RdRp contains the characteristic finger, palm, and thumb domains, as well as a unique N-terminal domain (NTD) that has never been observed. Mutagenesis studies on NS5B validated the importance of the NTD in the catalytic activity of this novel RNA-dependent RNA polymerase. Moreover, our results shed light on CSFV infection. Pigs are important domesticated animals. However, a highly contagious viral disease named classical swine fever (CSF) causes devastating economic losses. Classical swine fever virus (CSFV), the primary cause of CSF, is a positive-sense single-stranded RNA virus belonging to the genus , family Genome replication of CSFV depends on an RNA-dependent RNA polymerase (RdRp) known as NS5B. However, the structure of CSFV NS5B has never been reported, and the mechanism of CSFV replication is poorly understood. Here, we solve the first crystal structure of CSFV NS5B and analyze the functions of the characteristic finger, palm, and thumb domains. Additionally, our structure revealed the presence of a novel N-terminal domain (NTD). Biochemical studies demonstrated that the NTD of CSFV NS5B is very important for RdRp activity. Collectively, our studies provide a structural basis for future rational design of anti-CSFV drugs, which is critically important, as no effective anti-CSFV drugs have been developed.

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Different evolutionary patterns of classical swine fever virus envelope proteins

Yang

Zhang

2016

Can. J. Microbiol.

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Classical swine fever virus (CSFV) is the causative agent of classical swine fever, which is a highly contagious disease of the domestic pig as well as wild boar. The proteins Erns, E1, and E2 are components of the viral envelope membrane. They are also implicated in virus attachment and entry, replication, and (or) anti-immune response. Here, we studied the genetic variations of these envelope proteins in the evolution of CSFV. The results reveal that the envelope proteins underwent different evolutionary fates. In Erns and E1, but not E2, a number of amino acid sites experienced functional divergence. Furthermore, the diversification in Erns and E1 was generally episodic because the divergence-related changes of E1 only occurred with the separation of 2 major groups of CSFV and that of Erns took place with the division of 1 major group. The major divergence-related sites of Erns are located on one of the substrate-binding regions of the RNase domain and C-terminal extension. These functional domains have been reported to block activation of the innate immune system and attachment and entry into host cells, respectively. Our results may shed some light on the divergent roles of the envelope proteins.

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Episodic adaptive diversification of classical swine fever virus RNA-dependent RNA polymerase NS5B

Cited by 4 publications

References 42 publications

Adaptive Diversification Between Yellow Fever Virus West African and South American Lineages: A Genome-Wide Study

Adaptive Diversification Between Yellow Fever Virus West African and South American Lineages: A Genome-Wide Study

Crystal Structure of Classical Swine Fever Virus NS5B Reveals a Novel N-Terminal Domain

Different evolutionary patterns of classical swine fever virus envelope proteins

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