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Livestock farming across the world is constantly threatened by the evolutionary turnover of foot-and-mouth disease virus (FMDV) strains in endemic systems, the underlying dynamics of which remain to be elucidated. Here, we map the eco-evolutionary landscape of cocirculating FMDV lineages within an important endemic virus pool encompassing Western, Central, and parts of Southern Asia, reconstructing the evolutionary history and spatial dynamics over the last 20 years that shape the current epidemiological situation. We demonstrate that new FMDV variants periodically emerge from Southern Asia, precipitating waves of virus incursions that systematically travel in a westerly direction. We evidence how metapopulation dynamics drive the emergence and extinction of spatially structured virus populations, and how transmission in different host species regulates the evolutionary space of virus serotypes. Our work provides the first integrative framework that defines coevolutionary signatures of FMDV in regional contexts to help understand the complex interplay between virus phenotypes, host characteristics, and key epidemiological determinants of transmission that drive FMDV evolution in endemic settings.

Phylogenetic analyses of foot-and-mouth disease type A viruses in the Middle East during 2015-2016 identified viruses belonging to the A/ASIA/G-VII lineage, which originated in the Indian subcontinent. Changes in a critical antigenic site within capsid viral protein 1 suggest possible evolutionary pressure caused by an intensive vaccination program.

Phylogenetic studies on foot-and-mouth disease viruses (FMDVs) circulating in the West Eurasian region have largely focused on the genomic sequences encoding the structural proteins that determine the serotype. The present study has compared near-complete genome sequences of FMDVs representative of the viruses that circulate in this region. The near-complete genome sequences (ca. 7,600 nt) were generated from multiple overlapping RT-PCR products. These amplicons were from FMDVs belonging to serotypes O, A and Asia-1, including members of the O-PanAsia-II and the A-Iran05 lineages, and of Group-II and Group-VII (Sindh-08) within serotype Asia-1, which are currently predominant and widespread in West Eurasia. These new sequences were analysed together with other sequences obtained from GenBank. Comparison of different regions of the FMDVs genomes revealed evidence for multiple, inter-serotypic, recombination events between FMDVs belonging to the serotypes O, A and Asia-1. It is concluded from the present study that dramatic changes in virus sequences can occur in the field through recombination between different FMDV genomes. These analyses provide information about the ancestry of the serotype O, A and Asia-1 FMDVs that are currently circulating within the West Eurasian region.

Guvenc, Tolga/0000-0003-1468-3415; Parlak, Unal/0000-0003-2870-8345; GULBAHAR, MUSTAFA YAVUZ/0000-0001-8268-7659; /0000-0002-0636-4214 WOS: 000250060400003 PubMed: 17846231 The present study describes the pathogenetic mechanisms of myocarditis in 9 lambs that died in a foot-and-mouth disease outbreak in Samsun, Turkey. In all the heart samples tested, ELISA and sequencing for phylogenetic analyses showed that the virus, namely O/TUR/Samsun/05, was associated with the PanAsia pandemic strain of foot-and-mouth disease virus (FMDV) type O. The lambs had myocardial lesions but no typical vesicular lesions. In situ reverse transcription showed that many cardiomyocytes and some interstitial cells were positive for FMDV type O. Inflammatory infiltration, hyaline degeneration, and necrosis of sheets of myocytes were observed. The cellular infiltrates were mononuclear cells, including many lymphocytes, macrophages, a few plasma cells, and neutrophils. Major histocompatibility complex Class II+ dendritic and mononuclear cells, 76 T cells, CD172A+ and CD14+ macrophages and monocytes, and IgM+ B cells were detected mainly in the infected hearts. Inducible nitric oxide synthetase (NOS) was seen mostly in areas of inflammation infiltrated by large numbers of cells. Of the 2 alpha-subunits of integrin known to be used as receptors by FMDV in epithelial tissues, CD49e (integrin alpha 5) was detected in the membranes of cardiac myocytes with intercalated discs, but CD51 (integrin alpha V) was not detected in cardiac myocytes from infected or normal lambs. Interstitial and inflammatory cells were positive for both integrin subunits. The terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling (TUNEL)-positive signal was detected in the nuclei of both cardiac myocytes and interstitial cells from infected lambs. These findings suggest that the NOS expressed by inflammatory cells in lesions may have a deleterious effect on cardiac myocytes in these lesions.

Two genotypes of foot-and-mouth disease virus serotype A were identified as the cause of disease outbreaks in Turkey during 1996-2004, while serotype O strains, identified during the same period, seem to represent an evolutionary continuum, and Asia1 strains were only rarely identified. The data presented are concordant with the conclusion that serotype A strains are repeatedly introduced to Turkey from the east and circulate only transiently in farming communities, while type O strains persist and re-emerge from endemic areas of Turkey. The co-circulation of strains belonging to two A genotypes for 6 years, as observed in the present study, is a remarkable difference compared to previous decades in which only one A genotype was transiently circulating, successively being replaced by others. This co-circulation was observed in spite of enforcement countrywide of biannual vaccination of more than 50% of the cattle during the same period. Mean r(1) values of 0.70 +/- 0.19 and 0.39 +/- 0.04 found for A96 and A99 isolates, respectively, compared to the A96 vaccine component reveal antigenic differences but also imply that the vaccine in use in Turkey should provide protection against both genotypes. It is suggested that further studies to reveal the nature of the difference in epidemiological dynamics of type A and type O strains might lead to an understanding of the measures required to control foot-and-mouth disease in islands of persistent circulation.

This report describes the characterization of a new genotype of foot-and-mouth disease virus (FMDV) type A responsible for recent FMD outbreaks in the Middle East. Initially identified in samples collected in 2003 from Iran, during 2005 and 2006 this FMDV lineage (proposed to be named A-Iran-05) spread into Saudi Arabia and Jordan and then further west into Turkey reaching European Thrace in January 2007. Most recently A-Iran-05 has been found in Bahrain. To the east of Iran, it has been recognized in Afghanistan (2004-07) and Pakistan (2006-07). Throughout the region, this lineage is now the predominant genotype of FMDV serotype A sampled, and has appeared to have replaced the A-Iran-96 and A-Iran-99 strains which were previously encountered. In August 2007, a new A-Iran-05 sub-lineage (which we have called A-Iran-05(ARD-07)) was identified in Ardahan, Turkey, close to the border with Georgia. This new sub-lineage appeared to predominate in Turkey in 2008, but has, so far, not been identified in any other country. Vaccine matching tests revealed that the A-Iran-05 viruses are antigenically different to A-Iran-96 and more like A(22). These findings emphasize the importance of undertaking continued surveillance in the Middle East and Central Asia in order to detect and monitor the emergence and spread of new FMDV strains.

Background Foot-and-Mouth Disease (FMD) causes significant economic losses in Turkish livestock. We have analysed the genetic diversity of the 1D sequences, encoding the hypervariable surface protein VP1, of Turkish isolates of serotype A and O collected from 1998 to 2004 in order to obtain epidemiological and immunological information. Results The 1D coding region of 33 serotype O and 20 serotype A isolates, obtained from outbreaks of FMD between 1998 and 2004, was sequenced. For serotype A, we confirmed the occurrence of the two subtypes IRN99 and IRN96. These subtypes are most divergent within the region encoding the immuno-dominant GH-loop. Also a close relationship to Foot-and-Mouth Disease virus (FMDV) serotype A isolates obtained from outbreaks in Iraq and Iran were detected and a clustering of isolates collected during the same period of time were found. The analysis of the deduced amino-acid sequences of these subtypes revealed evidence of positive selection in one site and one deletion, both within the GH-loop region. By inferring the ancestral history of the positively selected codon, two potential precursors were found. Furthermore, the structural alignment of IRN99 and IRN96 revealed differences between the tertiary structures of these subtypes. The similarity plot of the serotype O isolates suggested a more homogeneous group than the serotype A isolates. However, phylogenetic analysis revealed two major groups, each further divided in subgroups, of which some only consisted of Turkish isolates. Positively selected sites and structural differences of the Turkish isolates analysed, were not found. Conclusion The sequence and structural analysis of the IRN99 strains is indicative of positive selection suggesting an immunological advantage compared to IRN96. However, results of antigenic comparison reported elsewhere do not substantiate such a conclusion. There is evidence that IRN99 was introduced to Turkey, in all probability from Iran. Since, a member of the IRN96 lineage was included as a component of the FMDV vaccine produced since 2000, the outbreaks caused by IRN96 strains in 2004 could be due to incomplete vaccine coverage. The Turkish type O strains, all with a VP1 structure similar to the O1/Manisa/69 vaccine, appear in several sublineages. Whether these sublineages reflect multiple samplings from a limited number of outbreaks, or if they reflect cross-boundary introductions is not clear.

FURTHER to the letter from Nigel Gibbens, the UK Chief Veterinary Officer ( VR , February 5, 2011, vol 168, pp 136–137), we would like to provide additional information about the recent appearance of foot-and-mouth disease (FMD) in south-eastern Bulgaria. Since the end of December 2010, three outbreaks of FMD have been reported in Burgas region, close to the border with Turkish Thrace, which is a FMD-free zone (with vaccination). Samples collected from the first recognised case, in wild boar shot near to Kosti village, Tsarevo Municipality, were tested locally at the National Reference Laboratory for FMD, Sofia, and …

Guvenc, Tolga/0000-0003-1468-3415; /0000-0002-0636-4214; Parlak, Unal/0000-0003-2870-8345; GULBAHAR, MUSTAFA YAVUZ/0000-0001-8268-7659 WOS: 000288473400010 PubMed: 21368565 This study describes the expression of heat shock protein70 (HSP70) and alpha-basic-crystallin (alpha-BC) and their association with apoptosis and some related adaptor proteins in the pathogenesis of foot-and-mouth disease virus (FMDV)-induced myocarditis in lambs. HSP70 was generally overexpressed in the myocardial tissues and inflammatory cells of FMDV-induced myocarditis with differential accumulation and localization in same hearts when compared to non-foot-and-mouth disease control hearts. a-BC immunolabeling showed coarse aggregations in the Z line of the cardiomyocytes in FMDV-infected hearts in contrast to control hearts. Overall, the results of this study show that the anti-apoptotic proteins, HSP70 and a-BC, were overexpressed with increased apoptosis in FMDV-infected heart tissues. Both proteins failed to protect the cardiomyocytes from apoptosis as defense mechanisms to the FMDV during the infection, suggesting that the virus is able to increase apoptosis via both downregulation and/or upregulation of these anti-apoptotic proteins.