Serro 2 Virus Highlights the Fundamental Genomic and Biological Features of a Natural Vaccinia Virus Infecting Humans.

Giliane Trindade,Bruno Fernandes Mota,Darin Carroll,Jônatas Abrahão,Ginny Emerson,Scott Sammons,Inger Damon,Flavio Guimarães Da Fonseca,Felipe De Assis,Cynthia Goldsmith,Melissa Olsen-Rasmussen,Erna Kroon,Yu Li,Michael Frace,Dhwani Govil

doi:10.3390/v8120328

Giliane Trindade, Bruno Fernandes Mota + Show 13 more

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https://doi.org/10.3390/v8120328

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Abstract

Vaccinia virus (VACV) has been implicated in infections of dairy cattle and humans, and outbreaks have substantially impacted local economies and public health in Brazil. During a 2005 outbreak, a VACV strain designated Serro 2 virus (S2V) was collected from a 30-year old male milker. Our aim was to phenotypically and genetically characterize this VACV Brazilian isolate. S2V produced small round plaques without associated comets when grown in BSC40 cells. Furthermore, S2V was less virulent than the prototype strain VACV-Western Reserve (WR) in a murine model of intradermal infection, producing a tiny lesion with virtually no surrounding inflammation. The genome of S2V was sequenced by primer walking. The coding region spans 184,572 bp and contains 211 predicted genes. Mutations in envelope genes specifically associated with small plaque phenotypes were not found in S2V; however, other alterations in amino acid sequences within these genes were identified. In addition, some immunomodulatory genes were truncated in S2V. Phylogenetic analysis using immune regulatory-related genes, besides the hemagglutinin gene, segregated the Brazilian viruses into two clusters, grouping the S2V into Brazilian VACV group 1. S2V is the first naturally-circulating human-associated VACV, with a low passage history, to be extensively genetically and phenotypically characterized.

Highlights

Vaccinia virus (VACV) is a poxvirus that has played a remarkable role in the history of science as the agent used to eradicate smallpox, the most deadly disease since the beginning of civilization [1].During the 1980s, VACV became the center of a new focus as possibilities emerged for its use in building expression vectors and recombinant vaccines [2]
Genome that encodes approximately 200 genes, which are distributed into a central region containing conserved genes involved in virus replication and an inverted terminal region (ITR), located at both termini containing, usually, less conserved genes related to the mechanisms of virus-host interactions, reflecting the co-evolution process between poxviruses and their many hosts [7]
No VACV outbreaks were recorded in that region prior to 2005

Summary

Introduction

During the 1980s, VACV became the center of a new focus as possibilities emerged for its use in building expression vectors and recombinant vaccines [2]. It is being used extensively for constructing recombinant vaccines for cancer and infectious diseases [2,3]. VACV replicates in the cytoplasm and can grow in vitro in many cell lines [4,5]. VACV produces infectious viral particles with different stages of maturation; the intracellular mature virus (IMV), the extracellular enveloped virus (EEV), and the cell-associated enveloped virus (CEV) [6]. Like other OPXV, VACV has a linear double-stranded DNA genome that encodes approximately 200 genes, which are distributed into a central region containing conserved genes involved in virus replication and an inverted terminal region (ITR), located at both termini containing, usually, less conserved genes related to the mechanisms of virus-host interactions, reflecting the co-evolution process between poxviruses and their many hosts [7]

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