Molecular analysis of the full-length F gene of Brazilian strains of canine distemper virus shows lineage co-circulation and variability between field and vaccine strains

Freitas, Luana Almeida; Leme, Raquel Arruda; Saporiti, Viviane; Alfieri, Amauri Alcindo

doi:10.1016/j.virusres.2019.02.009

Cited by 8 publications

(9 citation statements)

References 45 publications

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“…Due to external pressures on the host immune system, the H gene displays higher genetic variability when compared with other CDV genes 9 , which makes it suitable for lineage identification and phylogenetic analysis. Moreover, researchers have established that a short region of the F gene, which encodes the signal peptide of the F protein (Fsp), is extremely variable, suggesting that this region could also be a useful marker for evolutionary studies as it allows for the straightforward identification of CDV lineages 10–14 .…”

Section: Introductionmentioning

confidence: 99%

Phylogenetic evidence of the intercontinental circulation of a Canine distemper virus lineage in the Americas

Duque-Valencia

Forero-Muñoz²,

Díaz

et al. 2019

Sci Rep

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Canine distemper virus (CDV) is the cause of a multisystem disease in domestic dogs and wild animals, infecting more than 20 carnivore and non-carnivore families and even infecting human cell lines in in vitro conditions. Phylogenetic classification based on the hemagglutinin gene shows 17 lineages with a phylogeographic distribution pattern. In Medellín (Colombia), the lineage South America-3 is considered endemic. Phylogenetic studies conducted in Ecuador using fragment coding for the fusion protein signal peptide (Fsp) characterized a new strain belonging to a different lineage. For understanding the distribution of the South America-3 lineage in the north of the South American continent, we characterized CDV from three Colombian cities (Medellín, Bucaramanga, and Bogotá). Using phylogenetic analysis of the hemagglutinin gene and the Fsp region, we confirmed the circulation of CDV South America-3 in different areas of Colombia. We also described, for the first time to our knowledge, the circulation of a new lineage in Medellín that presents a group monophyletic with strains previously characterized in dogs in Ecuador and in wildlife and domestic dogs in the United States, for which we propose the name “South America/North America-4” due its intercontinental distribution. In conclusion, our results indicated that there are at least four different CDV lineages circulating in domestic dogs in South America: the Europe/South America-1 lineage circulating in Brazil, Uruguay, and Argentina; the South America-2 lineage restricted to Argentina; the South America-3 lineage, which has only been reported in Colombia; and lastly an intercontinental lineage present in Colombia, Ecuador, and the United States, referred to here as the “South America/North America-4” lineage.

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Section: Introductionmentioning

confidence: 99%

Phylogenetic evidence of the intercontinental circulation of a Canine distemper virus lineage in the Americas

Duque-Valencia

Forero-Muñoz²,

Díaz

et al. 2019

Sci Rep

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“…Few studies have analyzed molecular epidemiology and carried out molecular analysis of full-length genes from Brazilian CDV lineages 28 , 29 . Therefore, some researchers have performed complete sequence analysis of the full-length F and H genes 14 , 30 . These reports have demonstrated the predominance of one genotype in Brazil: SA1/EU.…”

Section: Discussionmentioning

confidence: 99%

“…Currently, there are at least 17 major CDV genetic lineages, including America-1 to America-5, Europe Wildlife, Arctic, South Africa, South America-1/Europe, South America-1 to South America-3, Rockborn-like, and Asia-1 to Asia-4 5 , 10 . Due to its greater genetic variability, the H and F genes have been the main choices for determining CDV genetic lineages 13 , 14 . In addition, these classifications are related to the geographic origin where the lineages have been detected.…”

Section: Introductionmentioning

confidence: 99%

“…To date, no studies have examined the full-length genome to characterize the Brazilian CDV field. Therefore, to elucidate the genetic basis of the protein diversity of CDV, we conducted amino acid and nucleotide sequence analysis of a recent field isolate, with a focus on the H and F genes, which are the most suitable targets to investigate the CDV variability and evolution 5 , 13 , 14 .…”

Section: Introductionmentioning

confidence: 99%

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First complete genome sequence and molecular characterization of Canine morbillivirus isolated in Central Brazil

Costa

Saivish

Oliveira

et al. 2021

Sci Rep

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The Brazilian regions are still highly endemic areas for Canine morbillivirus [canine distemper virus (CDV)]. However, little is known regarding the genetic variability of the strain circulating in several Brazilian regions. Here, we report the first full-length genome and molecular characterization of CDV isolated from domestic dogs in the Brazilian Center-West region. Sequence alignment and phylogenetic analyses based on deduced amino acid and nucleotide sequences showed that the isolated strain is characterized as the South America-I/Europe genotype. However, it segregates into a CDV subgenotype branch. Interestingly, both H and F proteins have a gain of a potential N-glycosylation sites compared to the Onderstepoort vaccine strain. Therefore, this study provides a reference to further understand the epidemic and molecular characteristics of the CDV in Brazil.

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“…However, CDV outbreaks in dogs and wildlife have been reported repeatedly, including dog populations with high rates of vaccine coverage [ 17 – 19 ]. There are high mutation rates for CDV, leading to changes in surface amino acids and resulting in antigenic divergence between vaccine and wild-type strains [ 20 – 22 ], which may be associated with some vaccine failures. These mutations also cause alterations of receptor binding specificity related to species barriers [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Multi-targeted gene silencing strategies inhibit replication of Canine morbillivirus

et al. 2020

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Background Canine morbilivirus (canine distemper virus, CDV) is a highly contagious pathogen associated with high morbidity and mortality in susceptible carnivores. Although there are CDV vaccines available, the disease poses a huge threat to dogs and wildlife hosts due to vaccine failures and lack of effective treatment. Thus, the development of therapeutics is an urgent need to achieve rapid outbreak control and reduce mortality in target species. Gene silencing by RNA interference has emerged as a promising therapeutic approach against different human and animal viruses. In this study, plasmid-based short hairpin RNAs (shRNAs) against three different regions in either CDV nucleoprotein (N), or large polymerase (L) genes and recombinant adenovirus-expressing N-specific multi-shRNAs were generated. Viral cytopathic effect, virus titration, plaque-forming unit reduction, and real-time quantitative RT-PCR analysis were used to check the efficiency of constructs against CDV. Results In CDV-infected VerodogSLAM cells, shRNA-expressing plasmids targeting the N gene markedly inhibited the CDV replication in a dose-dependent manner, with viral genomes and titers being decreased by over 99%. Transfection of plasmid-based shRNAs against the L gene displayed weaker inhibition of viral RNA level and virus yield as compared to CDV N shRNAs. A combination of shRNAs targeting three sites in the N gene considerably reduced CDV RNA and viral titers, but their effect was not synergistic. Recombinant adenovirus-expressing multiple shRNAs against CDV N gene achieved a highly efficient knockdown of CDV N mRNAs and successful inhibition of CDV replication. Conclusions We found that this strategy had strong silencing effects on CDV replication in vitro. Our findings indicate that the delivery of shRNAs using plasmid or adenovirus vectors potently inhibits CDV replication and provides a basis for the development of therapeutic strategies for clinical trials.

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Molecular analysis of the full-length F gene of Brazilian strains of canine distemper virus shows lineage co-circulation and variability between field and vaccine strains

Cited by 8 publications

References 45 publications

Phylogenetic evidence of the intercontinental circulation of a Canine distemper virus lineage in the Americas

Phylogenetic evidence of the intercontinental circulation of a Canine distemper virus lineage in the Americas

First complete genome sequence and molecular characterization of Canine morbillivirus isolated in Central Brazil

Multi-targeted gene silencing strategies inhibit replication of Canine morbillivirus

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