Bovine leucosis virus contamination of a vaccine produced in vivo against bovine babesiosis and anaplasmosis.

Contamination of a batch of tick fever (babesiosis and anaplasmosis) vaccine with bovine leucosis virus (BLV) was detected when a herd, in the final stages of an enzootic bovine leucosis (EBL) accreditation program, developed a large number of seropositive cattle following use of tick fever vaccine. Investigations incriminated a single calf used to produce Anaplasma centrale vaccine from which 13,959 doses were distributed. The failure of this calf to give a positive agar gel immunodiffusion (AGID) test before use was not fully explained. A total of 22,627 cattle from 111 herds receiving contaminated vaccine was tested to validate claims for compensation. Results showed infection rates of 62% and 51.8% in vaccinated dairy and beef cattle, respectively, compared with 6.1% and 1.5% in non-vaccinated cattle in the same herds. The results also indicated that infection did not spread from vaccinated to non-vaccinated in-contact cattle. Heavy reliance is now placed on purchase of calves for vaccine production from EBL accredited-free herds and on transmission tests from the calves to sheep to prevent a recurrence of contamination. The need for a BLV antigen detection test, with the sensitivity of the sheep transmission test but simpler and faster to perform, is evident.

Bovine leukaemia: facts and hypotheses derived from the study of an infectious cancer.

Bovine leukaemia virus (BLV) is the etiological agent of chronic lymphatic leukaemia/lymphoma in cows, sheep and goats. Infection without neoplastic transformation was also obtained in pigs, rhesus monkeys, chimpanzees, rabbits and observed in capybaras and water-buffaloes. Structurally and functionally, BLV is a relative of human T lymphotropic viruses 1 and 2 (HTLV-I and HTLV-II) In humans, HTLV-I induces a T-cell leukaemia and its type 2 counterpart has been found in dermatopathic lymphadenopathy, hairy T-cell leukaemia and prolymphocytic leukaemia cases. At variance with HTLV-I, BLV has not been associated with neurological diseases of the degenerative type. Bovine leukaemia virus, HTLV-I and HTLV-II show clearcut sequence homologies. The pathology of the BLV-induced disease, most notably the absence of chronic viraemia, a long latency period and lack of preferred proviral integration sites in tumours, is similar to that of adult T-cell leukaemia/lymphoma induced by HTLV-I. The most striking feature of these three naturally transmitted leukaemia viruses is the X region located between the env gene and the long terminal repeat (LTR) sequence. The X region contains several overlapping long open reading frames. One of them, designated XBL-I, encodes a trans-activator function capable of increasing the level of gene expression directed by BLV-LTR and most probably is involved in "genetic instability" of BLV-infected cells of the B cell lineage. The "genetic instability" renders the infected cell susceptible to move, along a number of stages, towards full malignancy. Little is known about these events and their causes; we present some theoretical possibilities. Bovine leukaemia virus infection has a worldwide distribution. In temperate climates, the virus spreads mostly via iatrogenic transfer of infected lymphocytes. In warm climates and in areas heavily populated by haematophagous insects, there are indications of insect-borne propagation of the virus.

Experimental transmission of bovine leukosis virus by simulated rectal palpation.

Eight six-month-old Holstein male calves were experimentally inoculated by rectal palpation with whole blood from a donor seropositive to bovine leukosis virus. The inoculation consisted of the deposition of 2 ml of whole blood on a disposable obstetrical sleeve followed by a 30 second rectal palpation to simulate the process of pregnancy detection or artificial insemination. This procedure was repeated at weekly intervals for three consecutive weeks. All eight calves developed antibodies to bovine leukosis virus within five weeks after the initial palpation. The presence of the virus was demonstrated in the peripheral blood leucocytes of all eight calves at nine weeks. These results indicated that routine rectal palpation may be an effective mode of spread of bovine leukosis virus in susceptible cattle.

Strong sequence conservation among horizontally transmissible, minimally pathogenic feline leukemia viruses.

We report the first complete nucleotide sequence (8,440 base pairs) of a biologically active feline leukemia virus (FeLV), designated FeLV-61E (or F6A), and the molecular cloning, biological activity, and env-long terminal repeat (LTR) sequence of another FeLV isolate, FeLV-3281 (or F3A). F6A corresponds to the non-disease-specific common-form component of the immunodeficiency disease-inducing strain of FeLV, FeLV-FAIDS, and was isolated from tissue DNA of a cat following experimental transmission of naturally occurring feline acquired immunodeficiency syndrome. F3A clones were derived from a subgroup-A-virus-producing feline tumor cell line. Both are unusual relative to other molecularly cloned FeLVs studied to date in their ability to induce viremia in weanling (8-week-old) cats and in their failure to induce acute disease. The F6A provirus is organized into 5'-LTR-gag-pol-env-LTR-3' regions; the gag and pol open reading frames are separated by an amber codon, and env is in a different reading frame. The deduced extracellular glycoproteins of F6A, F3A, and the Glasgow-1 subgroup A isolate of FeLV (M. Stewart, M. Warnock, A. Wheeler, N. Wilkie, J. Mullins, D. Onions, and J. Neil, J. Virol. 58:825-834, 1986) are 98% homologous, despite having been isolated from naturally infected cats 6 to 13 years apart and from widely different geographic locations. As a group, their envelope gene sequences differ markedly from those of the disease-associated subgroup B and acutely pathogenic subgroup C viruses. Thus, F6A and F3A correspond to members of a highly conserved family and represent prototypes of the horizontally transmitted, minimally pathogenic FeLV present in all naturally occurring infections.

Bovine leukemia: facts and hypotheses derived from the study of an infectious cancer.

Bovine leukemia virus is the etiological agent of a chronic lymphatic leukemia/lymphoma in cows, sheep, and goats. Infection without neoplastic transformation also was obtained in pigs, rhesus monkeys, chimpanzees, and rabbits, and was observed in capybaras and water buffaloes. Structurally and functionally, BLV is a relative of the human T lymphotropic viruses (HTLV-I and HTLV-II). HTLV-I induces in humans a T cell leukemia, and its type II counterpart has been found in dermatopathic lymphadenopathy, hairy T cell leukemia and prolymphocytic leukemia cases. At variance with HTLV-I, BLV has not been associated with neurological diseases of the degenerative type. BLV, HTLV-I, and HTLV-II show clearcut sequence homologies. The pathology of the BLV-induced disease, most notably, the absence of chronic viremia, a long latency period, and a lack of preferred proviral integration sites in tumors, is similar to that of adult T cell leukemia/lymphoma induced by HTLV-I. The most striking feature of the three naturally transmitted leukemia viruses is the X region located between the env gene and the LTR sequence. The X region contains several overlapping long open reading frames. One of them designated XBL-I encodes a trans-activator function capable of increasing the level of gene expression directed by BLV-LTR and most probably involved in "genetic instability" of BLV-infected cells of the B cell lineage. The genetic instability puts the cell into a context of fragility and ready to move along a number of stages towards full malignancy. Little is known about these events and their causes; we have presented some theoretical possibilities. BLV infection has a worldwide distribution. In temperate climates the virus spreads mostly via iatrogenic transfer of infected lymphocytes. In warm climates and in areas heavily populated by hematophageous insects, there are indications of insect-born propagation of the virus.

[Enzootic bovine leukosis--a retrovirus disease]. / Enzootische Rinderleukose--eine Retroviruskrankheit.

After a short historical introduction and a description of some of the properties of the bovine leucosis (leukemia) virus (BLV) the natural pathways of transmission, for which most likely intact infected cells are a prerequisite, are described and the role of possible vectors mentioned. The iatrogenic transmission by needles, dehorning and perhaps even rectal examinations is discussed. Semen, embryo transfer, saliva, urine, faeces and breath do obviously not play any role in contrast to nasal secretions containing viable cells. It is pointed out that it is not inevitable to eliminate all seropositive cattle from the premises during an eradication programme provided some additional tests are carried out: determination of the white blood picture, the p 24 status and perhaps even proof of antigen production in short-term buffy coat cultures. Offspring of seropositive cattle requires some special attention and careful testing at certain intervals. The report according to which BVD/MD virus-infected cattle are superinfected with BLV leading to rather difficult situations is cited.

Control of bovine leukosis virus in a dairy herd by a change in dehorning.

Following the demonstration that bovine leukosis virus was transmitted in calves by gouge dehorning, electrical dehorning at a younger age was implemented in a commercial Holstein herd. Subsequently, annual testing of the herd revealed a decline in the prevalence of bovine leukosis virus antibodies as older cattle dehorned by the former method were replaced by younger cattle dehorned by the latter method.

[Feline leukemia virus (FeLV) and FeLV-associated diseases in cats: a review]. / Kattenleukemievirus (FeLV) en FeLV-geassocieerde ziekten bij de kat: een overzicht.

Feline leukaemia virus (FeLV) usually occurs in its natural species, the domestic cat. FeLV is also important to human individuals as a comparative model, as FeLV may cause a variety of diseases which are partly malignant and partly benign, such as immunosuppression which bears a resemblance to AIDS (acquired immune deficiency syndrome) in man. Although FeLV is a common infective agent, the incidence of disease due to FeLV is much higher in cats kept in closed households in which several of them are present than it is in free-range cats. Consequently, diseases caused by FeLV are frequently diagnosed in pedigree cats which are often maintained in relatively large numbers. FeLV is transmitted among cats by contagion. The main sources of infection are persistantly infected FeLV carrier cats which continuously excrete virus from the mouth and in other secretions. The majority of cats infected with FeLV will produce neutralising antibodies. Cats which are unable to do so, will become permanently infected. The prognosis is bad in these cats: 90 per cent will die within five years. Various techniques are used to detect FeLV. The most common method, the indirect immunofluorescence (IFA) test, is performed on air-dried blood smears. The results of the IFA agree with that are almost completely identical to those of the virus isolation test. Another test is ELISA (enzyme-linked immunosorbent assay), which produces approximately 10 per cent more positive results which are probably due to circulating FeLV antigens. Dissemination of FeLV among cats may be prevented by identifying infected carrier cats and removing them from contact with non-infected cats. Removal programmes using indirect immunofluorescent antibody (IFA) tests were used successfully in the Netherlands. The proportion of FeLV-positive cats decreased from 9 per cent in 1974 to approximately 3 per cent in 1985 during such a removal programme. During the above period, the removal programme was carried out in the society of Dutch cat breeders 'Felikat', the programme being made compulsory on all members of the society. The incidence of cats positive for FeLV decreased from over 11 per cent in 1974 to less than 2 per cent within four years. None of the cats tested in this society was found to be positive for FeLV in 1984 and 1985. Besides removal programmes, other methods of control, such as vaccination, were developed to prevent the spread of FeLV. The FeLV-immunostimulating complex vaccine (FeLV-ISCOM vaccine) a subunit vaccine in which FeLV-gp70 is presented in a particular manner, seems to be promising.

In vitro viral expression as a criterion for development of control procedures for enzootic bovine leukosis.

In a university beef herd of 304 cattle in which six died of lymphosarcoma between 1980 and 1984, 77% of the Angus and 26% of the Charolais cattle were determined to be infected with bovine leukemia virus (BLV). Changes in iatrogenic procedures were initiated as early control measures. In vitro viral expression (VE) was used as a criterion to identify cattle for subsequent segregation or culling. This involved determinations of percentages of BLV-associated lymphocyte profiles among thin-sectioned Ficoll-Paque-isolated blood lymphocytes that were processed into plastic after culture for 48 h. Cattle retained until completion of nutritional studies or as breeding stock were separated into two groups. The BLV-seronegative cattle, BLV-seropositive cattle with 0% VE, and BLV-seropositive cattle with 1% to 4% VE were placed in group 1. Seropositive cattle with greater than or equal to 5% VE were placed in group 2. In 1985, evaluation of in vitro VE in 108 mature BLV-seropositive cattle retained for breeding revealed 36 (33%) had no observable VE. In 1986, 58 of 108 cattle were available to be reexamined, and 21 (36%) had 0% VE in both years. The VE expression values for individual cattle were generally comparable over the 2-year period. Of 48 initial seronegative breeding stock housed in group 1 with BLV-seropositive cattle with low or no VE, 21 (44%) seroconverted during 1985 to 1986. A positive correlation of 0.585 was found between VE and age-related absolute lymphocyte number.

Relationships of bovine leukemia virus prevalence in dairy herds and density of dairy cattle to human lymphocytic leukemia.

A case-control study was conducted to examine possible relationships between human acute lymphoid leukemia and exposure to dairy cattle and drinking of raw milk. Two hundred twenty-three persons with acute lymphoid leukemia, diagnosed during the years 1969 to 1971 and 1973 to 1980 from the 87 most rural Iowa counties, were accessed from case records at the Iowa State Health Registry for participation in the present study. Each person and 2 matched controls were interviewed for history of residence, exposure to dairy cattle, and consumption of nonpasteurized dairy products. Two types of comparisons between affected persons and controls were done: the prevalence of bovine leukemia virus infection (as measured by serologic study) in dairy herds with which the affected persons and controls had either occupational contact or from which they had consumed raw milk and the density of dairy cattle in the townships where affected persons and controls lived. The bovine leukemia virus infection prevalence in dairy herds with which affected persons had contact was 20%, whereas the infection prevalence in the herds with which the controls had contact was 38%. The density of dairy cows in townships where affected persons resided was generally less than that in townships where controls resided. However, there was one exception; the density of dairy cows at 20 years before diagnosis was higher (589) in townships where affected adult female persons resided, compared with that in townships where controls resided (567).

The zoonotic potential of feline leukemia virus.

The many studies that have addressed the possibility for FeLV infection in human beings are reviewed in this article. Because of the many similarities between FeLV-induced immune system impairment in cats and retrovirus related acquired immune deficiency syndrome in man, these two conditions are discussed as well.

Primary infection of Japanese infants with adult T-cell leukaemia-associated retrovirus (ATLV): evidence for viral transmission from mothers to children.

Primary infection with adult T-cell leukemia virus (ATLV) was investigated by follow-up studies on 16 ATLV-seropositive mothers and their breastfed infants in an ATLV-endemic area of Japan. Maternal antibody to ATLV decreased in all the infants, and was detectable in only three of 12 infants tested 6 months after birth. Reappearance of the antibody 9-18 months after birth was observed in only four of the 16 infants. The ATLV-bearing cells in peripheral blood were detected in all 16 mothers after delivery. None of the 16 infants showed ATLV-bearing cells in peripheral or cord blood sampled at birth, or 1, 3 or 6 months after birth. However, virus-bearing cells in the blood became detectable 9-18 months after birth in 13 of the 16 infants. Maternal antibody and virus-bearing cells were never detected in a control group of seven infants of ATLV-seronegative mothers. These findings provide evidence for the high incidence of primary ATLV infection during early infancy among infants born to ATLV-seropositive mothers and suggest maternal viral transmission. Furthermore, samples of breast milk from all 12 seropositive mothers examined contained cell-associated ATLV capable of being transmitted to peripheral leucocytes of neonates. This finding suggests that one of the possible maternal transmission routes of ATLV is via breast milk.