Virulence genetic markers in the LTR of naturally occurring variants of Bovine Leukemia Virus from Argentina

Virulence Genetic Markers in the LTR of Naturally Occurring Variants of Bovine Leukemia Virus from Argentina
*Sabrina M Rodríguez1 Karina G Trono1 Leandro R Jones1
1Instituto de Virología, CICVyA, INTA-Castelar, Castelar,
Buenos Aires, Argentina
*Corresponding author, Sabrina Rodríguez, E-mail: srodriguez@cnia.inta.gov.ar
Bovine leukemia virus (BLV), the causative agent of enzootic bovine leukosis, is classified within the Deltaretrovirus genus. The outcome of infection is diverse. Almost 70% of the infected animals are asymptomatic (AL), while 25% develop a benign condition called persistent lymphocytosis (PL). In addition, between 1 and 5% of the infected cattle develop a B-lymphoproliferative neoplastic condition or lymphosarcoma (LS). The genetic basis of these various clinical manifestations is unknown.
Long terminal repeats (LTR) are implicated in the regulation of viral and cellular gene expression. It is well documented for other retroviruses that even single point mutations in the nucleotidic sequence of the LTR can have a direct impact on tissue tropism, virulence, and pathogenicity. However, the influence of genetic variation in LTRs on clinical aspects has never been studied for BLV.
In order to study the association between LTR genetic variations and the clinical presentation of BLV infection, sequencing of the complete 5 -LTR region from 28 naturally BLV-infected cattle was carried out.
The relation of genetic variations to clinical evolution was analyzed for each variant position using comparative methods as implemented in Pagel’s correlation test of the Mesquite program. These analyses showed that two out of seven variant positions were highly correlated with pathogenesis (p value less than 10E-18).
The results reported herein suggest an important role for certain positions of the LTR in the determination of the clinical evolution of BLV-infected cattle. These findings could contribute to gaining insight into the molecular grounds of BLV viral pathogenesis in cattle.