The First Case of Bovine Astrovirus-Associated Encephalitis in the Southern Hemisphere (Uruguay), Uncovers Evidence of Viral Introduction to the Americas From Europe

Abstract

Astrovirus species members of the Mamastrovirus genus (family Astroviridae ) have been increasingly recognized as neuroinvasive pathogens in various mammals, including humans, mink, cattle, sheep, and pigs. While cases of astrovirus-associated encephalitis have been reported in North America, Europe, and Asia, their presence has never been documented in the Southern hemisphere. This paper describes a case of astrovirus-associated encephalitis in cattle in Uruguay that broadens the geographic distribution and genetic diversity of neuroinvasive astroviruses and provides phylogeographic evidence of viral introduction to the Americas from Europe. A 22-month-old Holstein steer from a farm in Colonia Department, Uruguay developed progressive neurological signs over a 3-days period before dying. Histopathological examination of the brain and proximal cervical spinal cord revealed disseminated, moderate to severe lymphocytic, histiocytic, and plasmacytic poliomeningoencephalomyelitis with neuronal necrosis. A Mamastrovirus strain in the CH13/NeuroS1 clade, that we called bovine astrovirus (BoAstV)-Neuro-Uy, was identified by reverse transcriptase PCR followed by nearly complete genome sequencing. Additionally, BoAstV was detected intralesionally in the brain by chromogenic RNA in situ hybridization within neuronal perikarya, axons and dendrites. Phylogenetic analysis of BoAstV-Neuro-Uy revealed a close relationship to neurotropic BoAstVs within the Virginia/Human-Mink-Ovine clade, which contains a growing cadre of neuroinvasive astroviruses. Analyzing the complete coding region of neuroinvasive BoAstVs sequences available in GenBank, we estimated an evolutionary rate of 4.27 × 10 -4 (95% HPD 2.19–6.46 × 10 -4 ) nucleotide substitutions/site/year. Phylogeographic analysis suggests that the common viral ancestor circulated in Europe between 1794–1940, and was introduced in Uruguay between 1849–1967, to later spread to North America and Japan.

The origin and past demography of murine astrovirus 1 in laboratory mice

“…The estimated mutation rate for RdRp was 2.6×10 −4 /site/year with 95 % highest posterior density (HPD) ranging from 3.3×10 −6 to 6.4×10 −4 /site/year. While the 95 % HPD was large, which is probably due to limited number of sequences analysed, the mean mutation rate was actually close to those derived from human or bovine astroviruses, ranging from 2.8 to 7.4×10 −4 / site /year [24][25][26], demonstrating our mutation rate estimation is authentic. The estimated mutation rate of the CP region was 6.2×10 −4 /site/year (95 % HPD 2.9×10 −5 to 1.3×10 −3 / site/year), which again fell well with the range of previously estimated astrovirus mutation rates.…”

Bovine Astrovirus Surveillance in Uruguay Reveals High Detection Rate of a Novel Mamastrovirus Species

“…The present survey showed a high prevalence of infection with a broad diversity of BoAstV. However, because there is great genetic diversity within the MAstV genus, and this may have implications in pathogenicity [17], further studies are needed to assess whether particular species in this genus are associated with enteric disease in cattle, as seems to be the case for bovine encephalitis linked to MAstV-13 [3,4]. To date, most BoAstVs are not assigned to any of the 19 MAstV species confirmed by the ICTV [9].…”

“…Evidence indicates that the BoAstVs that belong to MAstV-13 are associated with neurological diseases and encephalitis [3,4,20], while the other species are not clearly associated to disease, but are excreted in feces [11,13,18,22,23], and/or detected in nasopharyngeal exudates [5]. On the other hand, it is important to study the consequence of asymptomatic cases in the epidemiology and transmission of the virus [17].…”

“…In coinfections with other viruses, such as rotavirus and torovirus, the infectious capacity of BoAstV seems to be increased [2], although whether this is clinically relevant, or the virus plays a synergistic role in the development of diarrhea in cattle, needs further clarification. In 2013, the association of a genetically different lineage of BoAstV with neurologic disease and encephalomyelitis in cattle [3], which was recently described in Uruguay [4], resulted in increased interest in studying this group of viruses, along with their molecular epidemiology and pathogenicity. Recently, BoAstV was detected in 4/50 calves with bovine respiratory disease (BRD) and was absent in 50 asymptomatic calves in a case control study, but this viral infection was not statistically associated with BRD [5].…”

Astrovirus-Associated Polioencephalomyelitis in an Alpaca

“…Since then, they have been found worldwide in humans, especially in infants and children, suffering from gastroenteritis, and are among the most common pathogens to cause juvenile diarrhea [1][2][3][4]. In recent years, several studies have identified astrovirus-associated CNS infections in humans, mink, cattle, sheep, pigs, and a muskox [1,2,[5][6][7][8][9][10][11][12][13][14][15][16]. Remarkably, the majority of these neurotropic astroviruses phylogenetically cluster together in the so-called human-mink-ovine (HMO) clade, in which various enterotropic strains are also included [7,8].…”