Shuo Su

Evolutionary and genetic analysis of the VP2 gene of canine parvovirus

BackgroundCanine parvovirus (CPV) type 2 emerged in 1978 in the USA and quickly spread among dog populations all over the world with high morbidity. Although CPV is a DNA virus, its genomic substitution rate is similar to some RNA viruses. Therefore, it is important to trace the evolution of CPV to monitor the appearance of mutations that might affect vaccine effectiveness.ResultsOur analysis shows that the VP2 genes of CPV isolated from 1979 to 2016 are divided into six groups: GI, GII, GIII, GIV, GV, and GVI. Amino acid mutation analysis revealed several undiscovered important mutation sites: F267Y, Y324I, and T440A. Of note, the evolutionary rate of the CPV VP2 gene from Asia and Europe decreased. Codon usage analysis showed that the VP2 gene of CPV exhibits high bias with an ENC ranging from 34.93 to 36.7. Furthermore, we demonstrate that natural selection plays a major role compared to mutation pressure driving CPV evolution.ConclusionsThere are few studies on the codon usage of CPV. Here, we comprehensively studied the genetic evolution, codon usage pattern, and evolutionary characterization of the VP2 gene of CPV. The novel findings revealing the evolutionary process of CPV will greatly serve future CPV research.

One Health strategies for rabies control in rural areas of China

www.thelancet.com/infection Published online March 2, 2017 http://dx.doi.org/10.1016/S1473-3099(17)30116-0 1 rabies spread across borders (figure), and immunisation of wild animals and livestock might be the next challenge for China. Epidemiological surveys and phylogenetic analyses show that there are two levels of rabies control in China. The first level, the control of human rabies, is straightforward to implement. Strengthening of rabies prevention and vaccination in rural areas will be essential through the government, news organisations, and medical institutions. Public awareness of rabies in high-risk populations living in rural areas also needs to be improved. The second level is to eliminate rabies in wild animals and stray dogs, which will be important to address the reemergence of rabies in areas that were previously declared rabies free. More research on immunisation strategies and surveillance of rabies from wild animals and stray dogs is needed. Studies showed that domestic animals can be infected with rabies virus One Health strategies for rabies control in rural areas of China

Codon usage bias in the N gene of rabies virus

Since its emergence, rabies virus (RABV) has been a major worldwide concern especially in developing countries. The nucleoprotein (N) of RABV is highly conserved and key for genetic typing, thus a better understanding of the N gene evolutionary trajectory can assist the development of control measures. We found that the N gene of RABV has a low codon usage bias with a mean effective number of codons (ENC) value of 56.33 influenced by both mutation pressure and natural selection. However, neutrality analysis indicated that natural selection dominates over mutation pressure. Additionally, we found that dinucleotide bias partly contributed to RABV codon usage bias. On the other hand, based on the clades of phylogenetic tree, we found that the evolutionary rate of the Africa 2 clade was the highest with a mean value of 3.75×10-3 substitutions per site per year. Above all, our results regarding N gene of RABV codon usage will serve future RABV evolution research.

Genetic and evolutionary analysis of emerging H3N2 canine influenza virus

The H3N2 canine influenza virus (CIV) originated from an avian species. Since its emergence, it has circulated in multiple states and has caused pandemics among dog populations; however, no comprehensive studies have explored the causes driving these ongoing cases. The study of the codon usage patterns of viruses can reveal the genetic changes required for the viruses to adapt to new hosts and the external environment. Here we performed a thorough genetic, evolutionary, and codon usage analysis. We identified three evolutionary H3N2 CIV clades from a timescaled phylogenetic tree, namely, Origin, China, and Korea/USA, by principal component analysis (PCA). Additionally, we found a low codon usage bias and that mutation pressure, natural selection, and dinucleotide abundance shape the codon usage bias of H3N2 CIVs, with natural selection being more crucial than the others. Moreover, the human codon adaptation index was similar to that of dogs (the natural host) and cats. In addition, the H3N2 CIV similarity index values were higher than those of the avian influenza virus (AIV), suggesting viral adaptation to the host. Therefore, H3N2 CIVs may pose a potential risk to public health in the future, and further epidemiologic, evolutionary, and pathogenetic studies are required.

BECN1-dependent CASP2 incomplete autophagy induction by binding to rabies virus phosphoprotein

ABSTRACT Autophagy is an essential component of host immunity and used by viruses for survival. However, the autophagy signaling pathways involved in virus replication are poorly documented. Here, we observed that rabies virus (RABV) infection triggered intracellular autophagosome accumulation and results in incomplete autophagy by inhibiting autophagy flux. Subsequently, we found that RABV infection induced the reduction of CASP2/caspase 2 and the activation of AMP-activated protein kinase (AMPK)-AKT-MTOR (mechanistic target of rapamycin) and AMPK-MAPK (mitogen-activated protein kinase) pathways. Further investigation revealed that BECN1/Beclin 1 binding to viral phosphoprotein (P) induced an incomplete autophagy via activating the pathways CASP2-AMPK-AKT-MTOR and CASP2-AMPK-MAPK by decreasing CASP2. Taken together, our data first reveals a crosstalk of BECN1 and CASP2-dependent autophagy pathways by RABV infection.

Rabies virus matrix protein induces apoptosis by targeting mitochondria

Apoptosis, as an innate antiviral defense, not only functions to limit viral replication by eliminating infected cells, but also contribute to viral dissemination, particularly at the late stages of infection. A highly neurotropic CVS strain of rabies virus induces apoptosis both in vitro and in vivo. However, the detailed mechanism of CVS-mediated neuronal apoptosis is not entirely clear. Here, we show that CVS induces apoptosis through mitochondrial pathway by dissipating mitochondrial membrane potential, release of cytochrome c and AIF. CVS blocks Bax activation at the early stages of infection; while M protein partially targets mitochondria and induces mitochondrial apoptosis at the late stages of infection. The α-helix structure spanning 67-79 amino acids of M protein is essential for mitochondrial targeting and induction of apoptosis. These results suggest that CVS functions on mitochondria to regulate apoptosis at different stages of infection, so as to for viral replication and dissemination.

Insights into the genetic and host adaptability of emerging porcine circovirus 3

ABSTRACT Porcine circovirus 3 (PCV3) was found to be associated with reproductive disease in pigs, and since its first identification in the United States, it subsequently spread worldwide, especially in China, where it might pose a potential threat to the porcine industry. However, no exhaustive analysis was performed to understand its evolution in the prospect of codon usage pattern. Here, we performed a deep codon usage analysis of PCV3. PCV3 sequences were classified into two clades: PCV3a and PCV3b, confirmed by principal component analysis. Additionally, the degree of codon usage bias of PCV3 was slightly low as inferred from the analysis of the effective number of codons. The codon usage pattern was mainly affected by natural selection, but there was a co-effect of mutation pressure and dinucleotide frequency. Moreover, based on similarity index analysis, codon adaptation index analysis and relative codon deoptimization index analysis, we found that PCV3 might pose a potential risk to public health though with unknow pathogenicity. In conclusion, this work reinforces the systematic understanding of the evolution of PCV3, which was reflected by the codon usage patterns and fitness of this novel emergent virus.

Origin, Genetic Diversity, and Evolutionary Dynamics of Novel Porcine Circovirus 3

Abstract Porcine circovirus 3 (PCV3) is a novel virus associated with acute PDNS (porcine dermatitis and nephropathy syndrome)‐like clinical signs identified by metagenomic sequencing from swine. Its high occurrence may pose a potential threat to the swine industry worldwide. The processes resulting in the emergence and spread of PCV3 remain poorly understood. Herein, the possible origin, genotypes, and evolutionary dynamics of PCV3 based on available genomic sequences are determined. The closest ancestor of PCV3 is found to be within the clade 1 bat CVs. Using different phylogenetic methods, two major genotypes are identified, PCV3a and PCV3b. It is found that the effective population size of PCV3 increased rapidly during late 2013 to early 2014 and this is associated with the diversification of PCV3a and PCV3b. A relatively high effective reproductive number (Re) value and higher evolutionary rate were found compared to other single‐stranded DNA viruses, and positive selection on codons 122 and 320 (24 of ORF2) is identified. It is hypothesized that this, together with the prediction of a potential change of an antigenic epitope at position 320, might have allowed PCV3 to escape from the host immune response. Overall, this study has important implications for understanding the ongoing PCV3 cases worldwide and will guide future efforts to develop effective preventive and control measures.

Genetic diversity of porcine circovirus type 2 in China between 1999-2017

Porcine circovirus type 2 (PCV-2), is linked to PCV-2 associated disease, which has caused considerable economic loss in the swine industry. Here, we report the genetic diversity of PCV-2 in China. A total of 74 Chinese PCV-2 strains sequenced between 1999 and 2017 were studied. Based on the ORF2 and complete genomes, we found that apart from the PCV-2a, PCV-2b, and PCV-2d genotypes, two unstable recombination genotypes also exist, referred to as IM1 and IM2 genotypes. We found that the patterns of PCV-2 genetic shift in China are similar to the patterns at the global level. Additionally, for the PCV-2 ORF2 gene of Chinese isolates, we found a similar time to the most recent common ancestor and evolutionary rate to the global values. This indicates that PCV2 genetic diversity in China is driven by genetic drift/recombination of local strains and by the sporadic introduction of foreign genotypes from other countries. Overall, our study illustrates the genetic diversity and evolution dynamics of PCV-2 in China.

Comprehensive Analysis of Codon Usage on Rabies Virus and Other Lyssaviruses

Rabies virus (RABV) and other lyssaviruses can cause rabies and rabies-like diseases, which are a persistent public health threat to humans and other mammals. Lyssaviruses exhibit distinct characteristics in terms of geographical distribution and host specificity, indicative of a long-standing diversification to adapt to the environment. However, the evolutionary diversity of lyssaviruses, in terms of codon usage, is still unclear. We found that RABV has the lowest codon usage bias among lyssaviruses strains, evidenced by its high mean effective number of codons (ENC) (53.84 ± 0.35). Moreover, natural selection is the driving force in shaping the codon usage pattern of these strains. In summary, our study sheds light on the codon usage patterns of lyssaviruses, which can aid in the development of control strategies and experimental research.