Lentivirus-induced lymphoproliferative disease. Comparative pathogenicity of phenotypically distinct ovine lentivirus strains

Michael Dale Lairmore, J. M. Poulson, T. A. Adducci, J. C. DeMartini

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

For investigation of the pathogenicity of lentivirus strains, which have distinctly different cytopathic phenotypes in synovial membrane cell culture, plaque-purified, lytic, and nonlytic ovine lentivirus (OvLV) isolates were inoculated intratracheally into two groups of neonatal lambs. Twelve lambs were inoculated with a lytic OvLV isolate and 3 lambs each with two nonlytic OvLV isolates. Five control lambs were inoculated with either virus-free medium or were left uninoculated. In 8 of 12 lambs inoculated with a lytic OvLV isolate mild to severe lesion of lymphoid interstitial pneumonia (LIP) and pulmonary lymphoid hyperplasia developed, 6 of 12 lambs had lesions of pulmonary lymph node follicular hyperplasia, 3 of 9 female lambs had lesions of lymphoproliferative mastitis, 3 of 10 lambs had lesions of lymphocytic/plasmacytic synovitis, and 3 lambs had no lesions. In 3 of 6 lambs inoculated with nonlytic OvLV isolates only mild LIP lesions developed, without concurrent mammary gland or joint lesions. Bronchoalveolar lavage samples from OvLV-diseased lambs contained on average 1.5-fold more numbers of total leukocytes, and 4-fold more numbers of lymphocytes, compared with bronchoalveolar lavage samples of normal lambs. Monoclonal antibodies to ovine lymphocyte surface markers showed that the SBU-T8+ lymphocyte (CD 8 equivalent) was the predominant lymphocyte subset (mean of 65% of total lavaged lymphocytes) in bronchoalveolar lavage samples of 3 diseased lambs. Ovine lentivirus was reisolated from multiple tissues of both groups of OvLV-inoculated lambs, but the percentage of individual tissues infected was greater in lambs inoculated with the lytic viral isolate. Control lambs had no lesions and failed to produce OvLV-specific antibodies or yield OvLV from tissues. All OvLV-inoculated lambs produced either low or undetectable serum virus neutralizing antibodies. In contrast, lambs inoculated with either lytic or nonlytic OvLV produced precipitating antibodies to OvLV glycoprotein and group-specific protein. However, initial detection of precipitating antibodies to OvLV glycoprotein was earlier (mean, 5.8 weeks after inoculation) in OvLV-infected lambs in which severe lymphoproliferative disease developed and delayed (mean, 10.2 weeks after inoculation) in OvLV-infected lambs with mild or no lesions. Together, these results suggest that lentivirus isolates produced disease in a virus strain-dependent manner and suggest that humoral immune responses against OvLV failed to prevent lesion development in lentivirus-infected lambs. Pulmonary inoculation of neonatal lambs with a plaque-purified OvLV strain induced lymphoproliferative disease of the lung, mammary gland, and joints, suggesting that pathogenic lentivirus strains have multiple tissue tropisms and do not produce disease in a strictly organ-specific manner. The spectrum of pulmonary-associated lesions in lentivirus-inoculated lambs (lymphoid interstitial pneumonia, pulmonary lymphoid hyperplasia, and pulmonary lymph node follicular hyperplasia) were comparable to lymphoproliferative lung lesions reported in human immunodeficiency virus-infected children with acquired immunodeficiency syndrome.

Original languageEnglish (US)
Pages (from-to)80-90
Number of pages11
JournalAmerican Journal of Pathology
Volume130
Issue number1
StatePublished - 1988
Externally publishedYes

Fingerprint

Lentivirus
Virulence
Sheep
Lung
Hyperplasia
Bronchoalveolar Lavage
Human Mammary Glands
Viruses
Antibodies
Glycoproteins
Joints
Sheep Diseases
Lymph Nodes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Lentivirus-induced lymphoproliferative disease. Comparative pathogenicity of phenotypically distinct ovine lentivirus strains. / Lairmore, Michael Dale; Poulson, J. M.; Adducci, T. A.; DeMartini, J. C.

In: American Journal of Pathology, Vol. 130, No. 1, 1988, p. 80-90.

Research output: Contribution to journalArticle

@article{fbdb4faa80fa475b9411211f9f080f91,
title = "Lentivirus-induced lymphoproliferative disease. Comparative pathogenicity of phenotypically distinct ovine lentivirus strains",
abstract = "For investigation of the pathogenicity of lentivirus strains, which have distinctly different cytopathic phenotypes in synovial membrane cell culture, plaque-purified, lytic, and nonlytic ovine lentivirus (OvLV) isolates were inoculated intratracheally into two groups of neonatal lambs. Twelve lambs were inoculated with a lytic OvLV isolate and 3 lambs each with two nonlytic OvLV isolates. Five control lambs were inoculated with either virus-free medium or were left uninoculated. In 8 of 12 lambs inoculated with a lytic OvLV isolate mild to severe lesion of lymphoid interstitial pneumonia (LIP) and pulmonary lymphoid hyperplasia developed, 6 of 12 lambs had lesions of pulmonary lymph node follicular hyperplasia, 3 of 9 female lambs had lesions of lymphoproliferative mastitis, 3 of 10 lambs had lesions of lymphocytic/plasmacytic synovitis, and 3 lambs had no lesions. In 3 of 6 lambs inoculated with nonlytic OvLV isolates only mild LIP lesions developed, without concurrent mammary gland or joint lesions. Bronchoalveolar lavage samples from OvLV-diseased lambs contained on average 1.5-fold more numbers of total leukocytes, and 4-fold more numbers of lymphocytes, compared with bronchoalveolar lavage samples of normal lambs. Monoclonal antibodies to ovine lymphocyte surface markers showed that the SBU-T8+ lymphocyte (CD 8 equivalent) was the predominant lymphocyte subset (mean of 65{\%} of total lavaged lymphocytes) in bronchoalveolar lavage samples of 3 diseased lambs. Ovine lentivirus was reisolated from multiple tissues of both groups of OvLV-inoculated lambs, but the percentage of individual tissues infected was greater in lambs inoculated with the lytic viral isolate. Control lambs had no lesions and failed to produce OvLV-specific antibodies or yield OvLV from tissues. All OvLV-inoculated lambs produced either low or undetectable serum virus neutralizing antibodies. In contrast, lambs inoculated with either lytic or nonlytic OvLV produced precipitating antibodies to OvLV glycoprotein and group-specific protein. However, initial detection of precipitating antibodies to OvLV glycoprotein was earlier (mean, 5.8 weeks after inoculation) in OvLV-infected lambs in which severe lymphoproliferative disease developed and delayed (mean, 10.2 weeks after inoculation) in OvLV-infected lambs with mild or no lesions. Together, these results suggest that lentivirus isolates produced disease in a virus strain-dependent manner and suggest that humoral immune responses against OvLV failed to prevent lesion development in lentivirus-infected lambs. Pulmonary inoculation of neonatal lambs with a plaque-purified OvLV strain induced lymphoproliferative disease of the lung, mammary gland, and joints, suggesting that pathogenic lentivirus strains have multiple tissue tropisms and do not produce disease in a strictly organ-specific manner. The spectrum of pulmonary-associated lesions in lentivirus-inoculated lambs (lymphoid interstitial pneumonia, pulmonary lymphoid hyperplasia, and pulmonary lymph node follicular hyperplasia) were comparable to lymphoproliferative lung lesions reported in human immunodeficiency virus-infected children with acquired immunodeficiency syndrome.",
author = "Lairmore, {Michael Dale} and Poulson, {J. M.} and Adducci, {T. A.} and DeMartini, {J. C.}",
year = "1988",
language = "English (US)",
volume = "130",
pages = "80--90",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "1",

}

TY - JOUR

T1 - Lentivirus-induced lymphoproliferative disease. Comparative pathogenicity of phenotypically distinct ovine lentivirus strains

AU - Lairmore, Michael Dale

AU - Poulson, J. M.

AU - Adducci, T. A.

AU - DeMartini, J. C.

PY - 1988

Y1 - 1988

N2 - For investigation of the pathogenicity of lentivirus strains, which have distinctly different cytopathic phenotypes in synovial membrane cell culture, plaque-purified, lytic, and nonlytic ovine lentivirus (OvLV) isolates were inoculated intratracheally into two groups of neonatal lambs. Twelve lambs were inoculated with a lytic OvLV isolate and 3 lambs each with two nonlytic OvLV isolates. Five control lambs were inoculated with either virus-free medium or were left uninoculated. In 8 of 12 lambs inoculated with a lytic OvLV isolate mild to severe lesion of lymphoid interstitial pneumonia (LIP) and pulmonary lymphoid hyperplasia developed, 6 of 12 lambs had lesions of pulmonary lymph node follicular hyperplasia, 3 of 9 female lambs had lesions of lymphoproliferative mastitis, 3 of 10 lambs had lesions of lymphocytic/plasmacytic synovitis, and 3 lambs had no lesions. In 3 of 6 lambs inoculated with nonlytic OvLV isolates only mild LIP lesions developed, without concurrent mammary gland or joint lesions. Bronchoalveolar lavage samples from OvLV-diseased lambs contained on average 1.5-fold more numbers of total leukocytes, and 4-fold more numbers of lymphocytes, compared with bronchoalveolar lavage samples of normal lambs. Monoclonal antibodies to ovine lymphocyte surface markers showed that the SBU-T8+ lymphocyte (CD 8 equivalent) was the predominant lymphocyte subset (mean of 65% of total lavaged lymphocytes) in bronchoalveolar lavage samples of 3 diseased lambs. Ovine lentivirus was reisolated from multiple tissues of both groups of OvLV-inoculated lambs, but the percentage of individual tissues infected was greater in lambs inoculated with the lytic viral isolate. Control lambs had no lesions and failed to produce OvLV-specific antibodies or yield OvLV from tissues. All OvLV-inoculated lambs produced either low or undetectable serum virus neutralizing antibodies. In contrast, lambs inoculated with either lytic or nonlytic OvLV produced precipitating antibodies to OvLV glycoprotein and group-specific protein. However, initial detection of precipitating antibodies to OvLV glycoprotein was earlier (mean, 5.8 weeks after inoculation) in OvLV-infected lambs in which severe lymphoproliferative disease developed and delayed (mean, 10.2 weeks after inoculation) in OvLV-infected lambs with mild or no lesions. Together, these results suggest that lentivirus isolates produced disease in a virus strain-dependent manner and suggest that humoral immune responses against OvLV failed to prevent lesion development in lentivirus-infected lambs. Pulmonary inoculation of neonatal lambs with a plaque-purified OvLV strain induced lymphoproliferative disease of the lung, mammary gland, and joints, suggesting that pathogenic lentivirus strains have multiple tissue tropisms and do not produce disease in a strictly organ-specific manner. The spectrum of pulmonary-associated lesions in lentivirus-inoculated lambs (lymphoid interstitial pneumonia, pulmonary lymphoid hyperplasia, and pulmonary lymph node follicular hyperplasia) were comparable to lymphoproliferative lung lesions reported in human immunodeficiency virus-infected children with acquired immunodeficiency syndrome.

AB - For investigation of the pathogenicity of lentivirus strains, which have distinctly different cytopathic phenotypes in synovial membrane cell culture, plaque-purified, lytic, and nonlytic ovine lentivirus (OvLV) isolates were inoculated intratracheally into two groups of neonatal lambs. Twelve lambs were inoculated with a lytic OvLV isolate and 3 lambs each with two nonlytic OvLV isolates. Five control lambs were inoculated with either virus-free medium or were left uninoculated. In 8 of 12 lambs inoculated with a lytic OvLV isolate mild to severe lesion of lymphoid interstitial pneumonia (LIP) and pulmonary lymphoid hyperplasia developed, 6 of 12 lambs had lesions of pulmonary lymph node follicular hyperplasia, 3 of 9 female lambs had lesions of lymphoproliferative mastitis, 3 of 10 lambs had lesions of lymphocytic/plasmacytic synovitis, and 3 lambs had no lesions. In 3 of 6 lambs inoculated with nonlytic OvLV isolates only mild LIP lesions developed, without concurrent mammary gland or joint lesions. Bronchoalveolar lavage samples from OvLV-diseased lambs contained on average 1.5-fold more numbers of total leukocytes, and 4-fold more numbers of lymphocytes, compared with bronchoalveolar lavage samples of normal lambs. Monoclonal antibodies to ovine lymphocyte surface markers showed that the SBU-T8+ lymphocyte (CD 8 equivalent) was the predominant lymphocyte subset (mean of 65% of total lavaged lymphocytes) in bronchoalveolar lavage samples of 3 diseased lambs. Ovine lentivirus was reisolated from multiple tissues of both groups of OvLV-inoculated lambs, but the percentage of individual tissues infected was greater in lambs inoculated with the lytic viral isolate. Control lambs had no lesions and failed to produce OvLV-specific antibodies or yield OvLV from tissues. All OvLV-inoculated lambs produced either low or undetectable serum virus neutralizing antibodies. In contrast, lambs inoculated with either lytic or nonlytic OvLV produced precipitating antibodies to OvLV glycoprotein and group-specific protein. However, initial detection of precipitating antibodies to OvLV glycoprotein was earlier (mean, 5.8 weeks after inoculation) in OvLV-infected lambs in which severe lymphoproliferative disease developed and delayed (mean, 10.2 weeks after inoculation) in OvLV-infected lambs with mild or no lesions. Together, these results suggest that lentivirus isolates produced disease in a virus strain-dependent manner and suggest that humoral immune responses against OvLV failed to prevent lesion development in lentivirus-infected lambs. Pulmonary inoculation of neonatal lambs with a plaque-purified OvLV strain induced lymphoproliferative disease of the lung, mammary gland, and joints, suggesting that pathogenic lentivirus strains have multiple tissue tropisms and do not produce disease in a strictly organ-specific manner. The spectrum of pulmonary-associated lesions in lentivirus-inoculated lambs (lymphoid interstitial pneumonia, pulmonary lymphoid hyperplasia, and pulmonary lymph node follicular hyperplasia) were comparable to lymphoproliferative lung lesions reported in human immunodeficiency virus-infected children with acquired immunodeficiency syndrome.

UR - http://www.scopus.com/inward/record.url?scp=0023835529&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023835529&partnerID=8YFLogxK

M3 - Article

VL - 130

SP - 80

EP - 90

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 1

ER -