Early events following bovine leukaemia virus infection in calves with different alleles of the major histocompatibility complex DRB3 gene.

Cattle maintaining a low proviral load (LPL) status after bovine leukaemia virus (BLV) infection have been recognized as BLV controllers and non-transmitters to uninfected cattle in experimental and natural conditions. LPL has been associated with host genetics, mainly with the BoLA class II DRB3 gene. The aim of this work was to study the kinetics of BLV and the host response in Holstein calves carrying different BoLA-DRB3 alleles. Twenty BLV-free calves were inoculated with infected lymphocytes. Two calves were maintained uninfected as controls. Proviral load, total leukocyte and lymphocyte counts, anti-BLVgp51 titres and BLVp24 expression levels were determined in blood samples at various times post-inoculation. The viral load peaked at 30 days post-inoculation (dpi) in all animals. The viral load decreased steadily from seroconversion (38 dpi) to the end of the study (178 dpi) in calves carrying a resistance-associated allele (*0902), while it was maintained at elevated levels in calves with *1501 or neutral alleles after seroconversion. Leukocyte and lymphocyte counts and BLVp24 expression did not significantly differ between genetic groups. Animals with < 20 proviral copies/30 ng of DNA at 178 dpi or < 200 proviral copies at 88 dpi were classified as LPL, while calves with levels above these limits were considered to have high proviral load (HPL) profiles. All six calves with the *1501 allele progressed to HPL, while LPL was attained by 6/7 (86%) and 2/6 (33%) of the calves with the *0902 and neutral alleles, respectively. One calf with both *0902 and *1501 developed LPL. This is the first report of experimental induction of the LPL profile in cattle.

Co-infection with Mycobacterium bovis does not alter the response to bovine leukemia virus in BoLA DRB3*0902, genetically resistant cattle.

High proviral load (HPL) profile in bovine leukemia virus infected animals poses increased risk of transmission, and development of HPL or low proviral load (LPL) profile may be attributed to host genetics. Genetic resistance and susceptibility has been mapped to the Major Histocompatibility Complex class II DRB3 gene (BoLA DRB3). The aim of this work was to determine the effect of Mycobacterium bovis infection on certain virological and host immunological parameters of BLV experimental infection. Twenty-six Argentinian Holstein calves carrying the resistance-associated marker allele BoLA DRB3*0902, susceptibility-associated marker allele BoLA DRB3*1501, or neutral BoLA DRB3 alleles, exposed to M. bovis were used. Twenty calves were inoculated with BLV, three were naturally infected and other three were BLV-negative. Seven from twenty six (27%) of the animals resulted positive to the PPD test. The proviral load, absolute leukocyte and lymphocyte counts, time to seroconversion, antibody titer against BLV, and viral antigen expression in vitro at various times post inoculation were determined and compared between PPD+ and PPD- animals. From a total of 23 BLV positive animals (naturally and experimentally infected), 13 (56.5%) developed HPL, and 10 (43.5%) developed LPL. None of the investigated parameters were affected by infection with M. bovis. We concluded that the ability of cattle carrying resistance-associated marker to control BLV and to progress towards a LPL phenotype was not altered by M. bovis co-infection.

Partial molecular characterization of different proviral strains of bovine leukemia virus.

Bovine leukemia virus (BLV)-infected cattle were classified by their proviral load into low and high proviral load profiles (LPL and HPL, respectively). Blood from these animals was used to infect sheep to obtain multiple identical copies of integrated provirus. An env fragment of BLV was amplified from all infected sheep and sequenced. The sequences that were obtained were compared to already published BLV genome sequence, resulting in three clusters. Mutations could not be attributed to the passage of provirus from cattle to sheep and subsequent amplification and sequencing. The description of two different proviral load profiles, the association of the BoLA-DRB3.2 0902 allele with the LPL profile, the availability of complete BLV sequences, and the comparison of a variable region of the env gene from carefully characterized cattle are still not enough to explain the presence of animals in every herd that are resistant to BLV dissemination.