Enzootic bovine leukosis (EBL) is caused by bovine leukemia virus (BLV) infection and significantly impacts the livestock industry. However, the control of BLV infection is intractable in several region of world, where BLV infection is highly prevalent, including Japan. Many studies focused on host factors relating to BLV transmissibility and pathogenesis to develop fundamental knowledge about control strategy of BLV infection. On the other hand, the viral factors have not analyzed compared with host factors, because the BLV genome is highly conserved compared with other retroviruses. However, in understanding of infectious disease, the both host and viral factors are needed to be analyzed. Thus, we focused on viral factors, genetic variation. First, we demonstrated that the spontaneous mutations in BLV genome could affect virus production in vitro and proviral load, which is related to BLV transmissibility and pathogenesis in BLV-infected cows. The finding showed that the limited substitutions have a potential for changing transmissibility and pathogenesis. Next, we analyzed whether the limited substitutions could be related to EBL development, and demonstrated that the high and low virulence strains could be mainly isolated from EBL-developed and non-EBL cattle, respectively. Therefore, our studies could show that the spontaneous mutations affect biological properties of BLV relating to BLV transmissibility and pathogenesis. This report introduces new approach about interpretation of BLV transmissibility and pathogenesis. The knowledge would be useful for development of novel control strategy in BLV infection.
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