Genome of Bovine Viral Diarrhea Virus (BVDV) Contaminating a Continuous LFBK-αVß6 Cell Line.

Here, we report the genome of bovine viral diarrhea virus 1 (BVDV-1) contaminating a continuous fetal bovine kidney cell line. The cell line (LFBK-αVß6) is used for the rapid isolation and serotyping of foot-and-mouth disease virus (FMDV). The sequence contains the full polyprotein-coding sequence and partial untranslated regions (UTRs).

Simultaneous and Staggered Foot-and-Mouth Disease Virus Coinfection of Cattle.

Foot-and-mouth disease (FMD) field studies have suggested the occurrence of simultaneous infection of individual hosts by multiple virus strains; however, the pathogenesis of foot-and-mouth disease virus (FMDV) coinfections is largely unknown. In the current study, cattle were experimentally exposed to two FMDV strains of different serotypes (O and A). One cohort was simultaneously infected with both viruses, while additional cohorts were initially infected with FMDV A and subsequently superinfected with FMDV O after 21 or 35 days. Coinfections were confirmed during acute infection, with both viruses concurrently detected in blood, lesions, and secretions. Staggered exposures resulted in overlapping infections as convalescent animals with persistent subclinical FMDV infection were superinfected with a heterologous virus. Staggering virus exposure by 21 days conferred clinical protection in six of eight cattle, which were subclinically infected following the heterologous virus exposure. This effect was transient, as all animals superinfected at 35 days post-initial infection developed fulminant FMD. The majority of cattle maintained persistent infection with one of the two viruses while clearing the other. Analysis of viral genomes confirmed interserotypic recombination events within 10 days in the upper respiratory tract of five superinfected animals from which the dominant genomes contained the capsid coding regions of the O virus and nonstructural coding regions of the A virus. In contrast, there were no dominant recombinant genomes detected in samples from simultaneously coinfected cattle. These findings inculpate persistently infected carriers as potential FMDV mixing vessels in which novel strains may rapidly emerge through superinfection and recombination. IMPORTANCE Foot-and-mouth disease (FMD) is a viral infection of livestock of critical socioeconomic importance. Field studies from areas of endemic FMD suggest that animals can be simultaneously infected by more than one distinct variant of FMD virus (FMDV), potentially resulting in emergence of novel viral strains through recombination. However, there has been limited investigation of the mechanisms of in vivo FMDV coinfections under controlled experimental conditions. Our findings confirmed that cattle could be simultaneously infected by two distinct serotypes of FMDV, with different outcomes associated with the timing of exposure to the two different viruses. Additionally, dominant interserotypic recombinant FMDVs were discovered in multiple samples from the upper respiratory tracts of five superinfected animals, emphasizing the potential importance of persistently infected FMDV carriers as sources of novel FMDV strains.

Novel Recombinant Foot-and-Mouth Disease Virus Circulating in Vietnam.

We report the genome sequences of 12 recombinant foot-and-mouth disease virus isolates from Vietnam. The recombinant strain has a capsid region from an A/Sea-97 strain and a nonstructural segment from an O/ME-SA/PanAsia strain. The isolates were obtained from two outbreak samples collected in June 2017 and 10 subclinical samples collected between 2017 and 2019.

Genome Sequences of Seven Foot-and-Mouth Disease Virus Isolates Reveal Diversity in the O/ME-SA/Ind2001 Lineage in India between 1997 and 2009.

We report the genome sequences of seven foot-and-mouth disease (FMD) virus (FMDV) isolates collected in India between 1997 and 2009. The strains represented four sublineages within the O/ME-SA/Ind2001 lineage. These viruses provide insights into FMDV diversity and evolution in India and may influence future control measures, including vaccine selections.

Characterization of transboundary foot-and-mouth disease viruses in Nigeria and Cameroon during 2016.

Continuous surveillance for foot-and-mouth disease (FMD) in endemic settings such as West Africa is imperative to support improved local and regional control plans, with the long-term goal of regional eradication. This paper describes the genetic characterization of FMD viruses (FMDV) obtained from outbreaks in Nigeria (n = 45) and Cameroon (n = 15) during 2016 and from archival samples (n = 3) retrieved from a 2014 outbreak in Nigeria. These viruses were analysed in the context of previously published FMDV sequences from the region. Four FMDV serotypes: O, A, SAT1 and SAT2, were detected. Phylogenetic analyses of the VP1 coding sequences indicate the continuity of FMDV serotype O East Africa-3 (O/EA-3), serotype A AFRICA genotype G-IV (A/AFRICA/G-IV) and serotype South African Territories (SAT) 2 lineage VII (SAT2/VII). The FMDV SAT1 topotype X (SAT1/X), which emerged in Nigeria in 2015, continued to be associated with outbreaks in the region during 2016, and SAT1 is reported for the first time from Cameroon. Additionally, a re-emergence or re-introduction of the serotype O West Africa (O/WA) topotype in Nigeria is described herein. Our findings indicate a consistent, pan-serotypic relationship between FMDV strains detected in Cameroon and Nigeria. Additionally, FMDV strains from West Africa obtained in this study were genetically related to those occurring in East and North Africa. These phylogenetic relationships suggest that animal movements (pastoralism and/or trade) are important factors for virus spread across the African continent. These data provide critical baselines which are a necessary component of Stages 0 and 1 of the Progressive Control Pathway of FMD (PCP-FMD). Specifically, characterizing the existing virus strains (risk) provides the basis for the comprehensive risk-based control plan which is the requisite criteria for Nigeria's transition to Stage 2 of PCP-FMD, and for coordinated regional control of FMD.

Near-Full-Length Genome Sequence of a Foot-and-Mouth Disease Virus of Serotype Southern African Territories 2 Isolated from Nigeria in 2014.

We report a near-full-length genome sequence of a foot-and-mouth disease virus (FMDV) of serotype Southern African Territories 2 (SAT 2), topotype VII, isolated from cattle during an FMDV outbreak in Bauchi State, Nigeria, in October 2014. This provides the first SAT 2 near-full-length genome sequence from West Africa and contributes to our understanding of viral spread and evolution.

Genome Sequences of 18 Foot-and-Mouth Disease Virus Outbreak Strains of Serotype O Sublineage Ind2001d from India, 2013 to 2014.

We report the full polyprotein-coding sequences and partial untranslated regions (UTRs) of 18 foot-and-mouth disease (FMD) viruses from 4 outbreaks in India in 2013 and 2014. All strains grouped within the O/ME-SA/Ind2001d sublineage. These genomes update knowledge of FMD virus (FMDV) diversity in South Asia and may contribute to molecular epidemiology studies and vaccine selections.

First Genome Sequence of Foot-and-Mouth Disease Virus Serotype O Sublineage Ind2001e from Southern Vietnam.

We report the polyprotein coding sequence of the newly defined Ind2001e sublineage of foot-and-mouth disease virus (FMDV) serotype O, isolated from a bovine epithelial tissue sample collected in 2017 in Kon Tum Province, Vietnam. This discovery updates FMDV diversity in Vietnam, has implications for FMDV epidemiology, and influences future vaccine selections.

First Detection and Genome Sequence of Senecavirus A in Vietnam.

In 2018, senecavirus A was detected for the first time in Vietnam. This report contains the first complete genome of a senecavirus A isolate collected from pigs in Kon Tum Province, Vietnam. This novel incursion has substantial implications for regional control of vesicular transboundary diseases.

Contact Challenge of Cattle with Foot-and-Mouth Disease Virus Validates the Role of the Nasopharyngeal Epithelium as the Site of Primary and Persistent Infection.

The pathogenesis of foot-and-mouth disease virus (FMDV) in cattle was investigated through early and late stages of infection by use of an optimized experimental model for controlled contact exposure. Time-limited exposure of cattle to FMDV-infected pigs led to primary FMDV infection of the nasopharyngeal mucosa in both vaccinated and nonvaccinated cattle. In nonvaccinated cattle, the infection generalized rapidly to cause clinical disease, without apparent virus amplification in the lungs prior to establishment of viremia. Vaccinated cattle were protected against clinical disease and viremia; however, all vaccinated cattle were subclinically infected, and persistent infection occurred at similarly high prevalences in both animal cohorts. Infection dynamics in cattle were consistent and synchronous and comparable to those of simulated natural and needle inoculation systems. However, the current experimental model utilizes a natural route of virus exposure and is therefore superior for investigations of disease pathogenesis and host response. Deep sequencing of viruses obtained during early infection of pigs and cattle indicated that virus populations sampled from sites of primary infection were markedly more diverse than viruses from vesicular lesions of cattle, suggesting the occurrence of substantial bottlenecks associated with vesicle formation. These data expand previous knowledge of FMDV pathogenesis in cattle and provide novel insights for validation of inoculation models of bovine FMD studies.IMPORTANCE Foot-and-mouth disease virus (FMDV) is an important livestock pathogen that is often described as the greatest constraint to global trade in animal products. The present study utilized a standardized pig-to-cow contact exposure model to demonstrate that FMDV infection of cattle initiates in the nasopharyngeal mucosa following natural virus exposure. Furthermore, this work confirmed the role of the bovine nasopharyngeal mucosa as the site of persistent FMDV infection in vaccinated and nonvaccinated cattle. The critical output of this study validates previous studies that have used simulated natural inoculation models to characterize FMDV pathogenesis in cattle and emphasizes the importance of continued research of the unique virus-host interactions that occur within the bovine nasopharynx. Specifically, vaccines and biotherapeutic countermeasures designed to prevent nasopharyngeal infection of vaccinated animals could contribute to substantially improved control of FMDV.

Lack of Transmission of Foot-and-Mouth Disease Virus From Persistently Infected Cattle to Naïve Cattle Under Field Conditions in Vietnam.

Foot-and-mouth disease (FMD), caused by FMD virus (FMDV; Aphthovirus, Picornaviridae), is a highly contagious and economically important disease of cloven-hoofed domestic livestock and wildlife species worldwide. Subsequent to the clinical phase of FMD, a large proportion of FMDV-infected ruminants become persistently infected carriers, defined by detection of FMDV in oropharyngeal fluid (OPF) samples 28 days or more post-infection. The goal of this prospective study was to characterize the FMD carrier state in cattle subsequent to natural infection under typical husbandry practices in Vietnam. Ten persistently infected cattle on eight farms in the Long An province in southern Vietnam were monitored by monthly screening of serum and oropharyngeal fluid samples for 12 months. To assess transmission from FMDV carriers, 16 naïve cattle were intentionally brought into direct contact with the persistently infected animals for 6 months, and were monitored by clinical and laboratory methods. The restricted mean duration of the FMD carrier state was 27.7 months, and the rate of decrease of the proportion of carrier animals was 0.03 per month. There was no evidence of transmission to naïve animals throughout the study period. Additionally, there was no detection of FMDV infection or seroconversion in three calves born to carrier animals during the study. The force of infection for carrier-to-contact transmission was 0 per month, with upper 95% confidence limit of 0.064 per month. Phylogenetic analysis of viral protein 1 (VP1) coding sequences obtained from carriers indicated that all viruses recovered in this study belonged to the O/ME-SA/PanAsia lineage, and grouped phylogenetically with temporally and geographically related viruses. Analysis of within-host evolution of FMDV, based upon full-length open reading frame sequences recovered from consecutive samples from one animal, indicated that most of the non-synonymous changes occurred in Lpro, VP2, and VP3 protein coding regions. This study suggests that the duration of FMDV persistent infection in cattle may be longer than previously recognized, but the risk of transmission is low. Additional novel insights are provided into within-host viral evolution under natural conditions in an endemic setting.

Genome Sequences of Seven Foot-and-Mouth Disease Virus Isolates Collected from Serial Samples from One Persistently Infected Carrier Cow in Vietnam.

Several foot-and-mouth disease virus (FMDV) carrier cattle were identified in Vietnam by the recovery of infectious virus from oropharyngeal fluid. This report contains the first near-complete genome sequences of seven viruses from sequential samples from one carrier animal collected over the course of 1 year. The characterization of within-host viral evolution has implications for FMDV control strategies.

First detection of foot-and-mouth disease virus O/Ind-2001d in Vietnam.

In recent years, foot-and-mouth disease virus (FMDV) serotype O, topotype Middle East-South Asia (ME-SA), lineage Ind-2001d has spread from the Indian subcontinent to the Middle East, North Africa, and Southeast Asia. In the current report, we describe the first detection of this lineage in Vietnam in May, 2015 in Dak Nông province. Three subsequent outbreaks caused by genetically related viruses occurred between May-October, 2015 after which the virus was not detected in clinical outbreaks for at least 15 subsequent months. The observed outbreaks affected (in chronological order): cattle in Dak Nông province, pigs in Dak Lak province and Dak Nông province, and cattle in Ninh Thuan province. The clinical syndromes associated with these outbreaks were consistent with typical FMD in the affected species. Overall attack rate on affected premises was 0.85 in pigs and 0.93 in cattle over the course of the outbreak. Amongst 378 pigs at risk on affected premises, 85 pigs died during the outbreaks; there were no deaths among cattle. The manner in which FMDV/O/ME-SA/Ind-2001d was introduced into Vietnam remains undetermined; however, movement of live cattle is the suspected route. This incursion has substantial implications for epidemiology and control of FMD in Southeast Asia.