BACKGROUND
bovine leukemia virus  is highly endemic in many countries, including argentina  <cit> , where important economic losses result from fatal lymphosarcoma and restricted trade of genetic material.
because of the high prevalence, classical control measures, such as test and elimination and/or test and segregation, are not economically sustainable.
therefore, infection transmission should be decreased as much as practicable, to eventually reduce prevalence and drive the infection to extinction.
a feasible alternative, previously discussed  <cit> , could be achieved by eliminating animals with high proviral loads , most of them with persistent lymphocytosis   <cit> , and as consequence, with a higher probability of transmission of infection  <cit> , when compared to aleukemic  animals.
as prevention of spread from infected animals is of primary importance in breaking the cycle of blv transmission, it is important to know the pathophysiology of blv infection in young animals, as they are the main source of animal movement.
in this work, we followed the pvl and antibody  titers of infected newborn calves from birth to first parturition, to better understand blv infection evolution before calves enter the milking herd, when cattle are commingled and infection is likely to spread.
RESULTS
seven newborn infected calves were followed .
the pvls of five out of seven calves were low at birth.
all animals reached pvl levels of more than 1% infected peripheral blood mononuclear cells  ; three calves at 3 months, one calf at 6 months, and one calf at 12 months.
high pvls persisted until the end of the study .
calf # <dig> maintained a high pvl from birth until the end of the study  and calf # <dig> showed pvl fluctuations with a sporadic decrease under the pvl threshold of  <dig>  blv copies/cell at 3–6 months of age.
the pvl of calves # <dig> and # <dig> rose to more than  <dig> blv copy/cell.
antibody titers were  <dig> or higher in the first sample from all calves except for calf # <dig> that showed the lowest antibody titer at birth .
antibody titers decreased at 3–6 months to  <dig> or lower and then rose for the remainder of the study.
six calves  belonged to a dairy farm with a high blv prevalence; these represent 11% of the calves born in the herd during 2 months.
the dams of these calves had high pvl in blood   and high antibody titers  and detectable provirus  in the colostrum .
antibody levels detected in the calves’ blood confirmed good colostrum intake and antibody absorption corresponding to highest antibody titers in the group .
three animals could not be followed over the 36 months; animal # <dig> died at 18 months from unrelated causes, # <dig> was sold, and # <dig> was 2 years old at the conclusion of this study.
nd: not determined, sample not available, +: positive, -: negative.
discussion
we followed the dynamics of blv infection in calves that acquired infection during the first week of life.
while the study size is limited, our data show that perinatal infection can rapidly lead to pvls similar to highly infected adult cattle, and more than one copy of blv provirus per cell .
whether this is due to infection dose, animal age, or the mechanism of transmission remains unclear but suggests that newborn calves could become optimal blv propagators to neighboring cattle.
while we cannot confirm the infection source, the decay of antibodies at 3–6 months  suggests that infection was not acquired in utero but by contact during delivery or via consumption of infected colostrum or milk.
this is supported by the fact that all dams had high blood pvls and the majority had detectable provirus in colostrum , even in the presence of high antibody titers .
this finding is consonant with the data reported for human t-cell lymphotropic virus type- <dig> , a genetically and functionally related retrovirus, where high pvls in pregnant mothers are associated with a greater probability of transmitting the infection to children during delivery or by oral consumption of infected colostrum or milk  <cit> .
whether the infection is prenatal or postnatal, the rapid pvl rise suggests that the immune response does not stop viral replication.
this is supported by data that show that while the calf immune system is functional at birth, it is immature until at least 4 months of age  <cit> .
calves are immunosuppressed during the first week of life because of estrogen and cortisol produced by the dam before parturition and cortisol produced by the calf during parturition  <cit> .
some cytokines that regulate blv expression and delay progression to pl in adult cattle, including ifn-γ, il- <dig>  and il- <dig>  <cit> , are not efficiently expressed during the first week of life.
moreover, reduced levels of c3d  and the presence of maternal antibodies in serum may result in the suppression of neonatal b lymphocytes, by binding to their ligands cd <dig>  and cd <dig> , respectively  <cit> .
therefore, despite evidence of adequate colostrum intake and absorption , the adaptive and innate immune responses were not effective to maintain a balance between the response and the viral infection cycle, and, as a consequence, did not reach an equilibrium point within  <dig> to 8 months, as recently reported for experimentally inoculated adult sheep and cattle  <cit> .
this is critical in terms of viral transmission and infection epidemiology.
we speculate that viral burst cycles occur during the first few months of life in perinatally infected calves, allowing rapid transmission by contact to susceptible neighbors.
similar observations have been made in htlv- <dig>  <cit> .
moreover, patients infected with htlv- <dig> as children are more prone to develop clinical signs  <cit> .
while this was not detected in this study, a similar phenomenon could occur with blv.
from an epidemiological point of view, the presence of animals with high pvls is dangerous.
because it is a bloodborne pathogen, high levels of in vivo blv infection are associated with higher probability of transmission  <cit> .
because blv is highly endemic in dairy herds, classical control measures are not economically sustainable.
since blv infection produces serious economic losses due to fatal lymphosarcoma and trade restrictions, alternative programs must be developed to reduce the spread of infection and gradually decrease infection prevalence.
elimination of adult cattle with high pvls, along with movement of non-infected or low-infected heifers, may prove to be a feasible alternative, as previously discussed  <cit> .
however, this approach requires uninfected heifers for movement.
this study suggests that young infected animals represent a great risk for non-infected calves and could be a reason for the increased incidence before first parturition, when approximately half of pregnant heifers are already infected, 20–40% with high pvls  <cit> .
propagation could occur through iatrogenic procedures or even by contact with secretions or excretions that could be infected with the virus.
moreover, virus could transfer the maternal barrier when these animals are pregnant spreading the infection to the offspring.
a follow-up large-scale study with perinatally infected calves would be helpful to determine the prevalence of infection, range of pvls, monitor transmission, whether these animals are more prone to develop lymphosarcoma, and to monitor offspring and the related incidence of infection.
CONCLUSIONS
calves infected during the first week of life could play an active role in early propagation of blv to susceptible animals, since their pvl raised up during the first 12 months and persist as high for years.
early elimination could help to prevent transmission to young susceptible animals and to their own offspring.
to our knowledge, this is the first study of the kinetics of blv proviral load and antibody titers in newborn infected calves.

 bovine leukemia virus is highly endemic in many countries, including argentina, where important economic losses result from fatal lymphosarcoma and restricted trade of genetic material. because of the high prevalence, classical control measures, such as test and elimination and/or test and segregation, are not economically sustainable. therefore, infection transmission should be decreased as much as practicable, to eventually reduce prevalence and drive the infection to extinction. a feasible alternative, previously discussed, could be achieved by eliminating animals with high proviral loads, most of them with persistent lymphocytosis, and as consequence, with a higher probability of transmission of infection, when compared to aleukemic animals. as prevention of spread from infected animals is of primary importance in breaking the cycle of blv transmission, it is important to know the pathophysiology of blv infection in young animals, as they are the main source of animal movement. in this work, we followed the pvl and antibody titers of infected newborn calves from birth to first parturition, to better understand blv infection evolution before calves enter the milking herd, when cattle are commingled and infection is likely to spread.  seven newborn infected calves were followed. the pvls of five out of seven calves were low at birth. all animals reached pvl levels of more than 1% infected peripheral blood mononuclear cells; three calves at 3 months, one calf at 6 months, and one calf at 12 months. high pvls persisted until the end of the study. calf # maintained a high pvl from birth until the end of the study and calf # showed pvl fluctuations with a sporadic decrease under the pvl threshold of blv copies/cell at 3–6 months of age. the pvl of calves # and # rose to more than blv copy/cell. antibody titers were or higher in the first sample from all calves except for calf # that showed the lowest antibody titer at birth. antibody titers decreased at 3–6 months to or lower and then rose for the remainder of the study. six calves belonged to a dairy farm with a high blv prevalence; these represent 11% of the calves born in the herd during 2 months. the dams of these calves had high pvl in blood and high antibody titers and detectable provirus in the colostrum. antibody levels detected in the calves’ blood confirmed good colostrum intake and antibody absorption corresponding to highest antibody titers in the group. three animals could not be followed over the 36 months; animal # died at 18 months from unrelated causes, # was sold, and # was 2 years old at the conclusion of this study. nd: not determined, sample not available, +: positive, -: negative. discussion we followed the dynamics of blv infection in calves that acquired infection during the first week of life. while the study size is limited, our data show that perinatal infection can rapidly lead to pvls similar to highly infected adult cattle, and more than one copy of blv provirus per cell. whether this is due to infection dose, animal age, or the mechanism of transmission remains unclear but suggests that newborn calves could become optimal blv propagators to neighboring cattle. while we cannot confirm the infection source, the decay of antibodies at 3–6 months suggests that infection was not acquired in utero but by contact during delivery or via consumption of infected colostrum or milk. this is supported by the fact that all dams had high blood pvls and the majority had detectable provirus in colostrum, even in the presence of high antibody titers. this finding is consonant with the data reported for human t-cell lymphotropic virus type-, a genetically and functionally related retrovirus, where high pvls in pregnant mothers are associated with a greater probability of transmitting the infection to children during delivery or by oral consumption of infected colostrum or milk. whether the infection is prenatal or postnatal, the rapid pvl rise suggests that the immune response does not stop viral replication. this is supported by data that show that while the calf immune system is functional at birth, it is immature until at least 4 months of age. calves are immunosuppressed during the first week of life because of estrogen and cortisol produced by the dam before parturition and cortisol produced by the calf during parturition. some cytokines that regulate blv expression and delay progression to pl in adult cattle, including ifn-γ, il- and il-, are not efficiently expressed during the first week of life. moreover, reduced levels of c3d and the presence of maternal antibodies in serum may result in the suppression of neonatal b lymphocytes, by binding to their ligands cd and cd, respectively. therefore, despite evidence of adequate colostrum intake and absorption, the adaptive and innate immune responses were not effective to maintain a balance between the response and the viral infection cycle, and, as a consequence, did not reach an equilibrium point within to 8 months, as recently reported for experimentally inoculated adult sheep and cattle. this is critical in terms of viral transmission and infection epidemiology. we speculate that viral burst cycles occur during the first few months of life in perinatally infected calves, allowing rapid transmission by contact to susceptible neighbors. similar observations have been made in htlv-. moreover, patients infected with htlv- as children are more prone to develop clinical signs. while this was not detected in this study, a similar phenomenon could occur with blv. from an epidemiological point of view, the presence of animals with high pvls is dangerous. because it is a bloodborne pathogen, high levels of in vivo blv infection are associated with higher probability of transmission. because blv is highly endemic in dairy herds, classical control measures are not economically sustainable. since blv infection produces serious economic losses due to fatal lymphosarcoma and trade restrictions, alternative programs must be developed to reduce the spread of infection and gradually decrease infection prevalence. elimination of adult cattle with high pvls, along with movement of non-infected or low-infected heifers, may prove to be a feasible alternative, as previously discussed. however, this approach requires uninfected heifers for movement. this study suggests that young infected animals represent a great risk for non-infected calves and could be a reason for the increased incidence before first parturition, when approximately half of pregnant heifers are already infected, 20–40% with high pvls. propagation could occur through iatrogenic procedures or even by contact with secretions or excretions that could be infected with the virus. moreover, virus could transfer the maternal barrier when these animals are pregnant spreading the infection to the offspring. a follow-up large-scale study with perinatally infected calves would be helpful to determine the prevalence of infection, range of pvls, monitor transmission, whether these animals are more prone to develop lymphosarcoma, and to monitor offspring and the related incidence of infection.  calves infected during the first week of life could play an active role in early propagation of blv to susceptible animals, since their pvl raised up during the first 12 months and persist as high for years. early elimination could help to prevent transmission to young susceptible animals and to their own offspring. to our knowledge, this is the first study of the kinetics of blv proviral load and antibody titers in newborn infected calves. 
all animals reached pvls of more than 1% infected peripheral blood mononuclear cells, three at 3 months, one at 6 months, and one at 12 months. to our knowledge, this is the first study of the kinetics of blv proviral load and antibody titers in newborn infected calves. early elimination could help to prevent transmission to young susceptible animals and to their own offspring. bovine leukemia virus is highly endemic in many countries, including argentina. high pvls persisted until the end of the study, and, in two animals, exceeded one blv copy per cell. as prevention of the spread from infected animals is of primary importance in breaking the cycle of blv transmission, it is important to know the pathophysiology of blv infection in young animals, as they are the main source of animal movement. calves infected during the first week of life could play an active role in early propagation of blv to susceptible animals, since their pvl raised up during the first 12 months and persist as high for years. two other calves maintained a high pvl from birth until the end of the study. in this work, we determined the proviral load and antibody titers of infected newborn calves from birth to first parturition. all calves under study were born to infected dams with high proviral load in blood and high antibody titers and detectable provirus in the colostrum. antibody titers were or higher in the first sample from six out of seven calves.
 bovine leukemia virus is highly endemic in many countries, including argentina. as prevention of the spread from infected animals is of primary importance in breaking the cycle of blv transmission, it is important to know the pathophysiology of blv infection in young animals, as they are the main source of animal movement. in this work, we determined the proviral load and antibody titers of infected newborn calves from birth to first parturition.  all calves under study were born to infected dams with high proviral load in blood and high antibody titers and detectable provirus in the colostrum. the pvl for five out of seven calves was low at birth. all animals reached pvls of more than 1% infected peripheral blood mononuclear cells, three at 3 months, one at 6 months, and one at 12 months. high pvls persisted until the end of the study, and, in two animals, exceeded one blv copy per cell. two other calves maintained a high pvl from birth until the end of the study. antibody titers were or higher in the first sample from six out of seven calves. these decayed at 3–6 months to or lower, and then increased again after this point.  calves infected during the first week of life could play an active role in early propagation of blv to susceptible animals, since their pvl raised up during the first 12 months and persist as high for years. early elimination could help to prevent transmission to young susceptible animals and to their own offspring. to our knowledge, this is the first study of the kinetics of blv proviral load and antibody titers in newborn infected calves. blvperinatal infectionproviral loadnatural infection 