The expression of gag (p15, p25) and env gene products in ovine lentivirus-infected cells was studied in 20 adult Texel ewes seropositive to maedi-visna virus and 10 seronegative matched controls. Bronchoalveolar lavage was performed to recover alveolar cell pools from which cytocentrifuge preparations were made, Single and double immunocytochemical techniques were applied to study viral replication and coexpression of viral markers with markers for macrophages, lymphocytes, and major histocompatibility complex (MHC) class II. Alveolar macrophages of eight of 20 infected sheep (40%) were positive for viral protein expression. The percentage of positive macrophages varied from < 1% to 12% of the total population of macrophages. Viral protein expression was not detected in lymphocytes or other cell types. A relationship between virus-replicating macrophages and differential expression of MHC class II molecules, upregulated in ovine lentivirus infection, could not be established. Pathology was evaluated in nine infected ewes. Animals with the highest levels of positive cells had moderate or severe lymphoid interstitial pneumonia. However, sheep with similar degrees of lesions had lower percentages of positive macrophages or were negative for viral protein detection. These results support the idea that a partial or even a complete loss in the restriction mechanism of maedi-visna virus in lungs can occur in some individuals.
AgostiniCPolettiVZambelloRTrentinLSivieroFSpigaLGrittiFSemenzatoG:
Phenotypical and functional analysis of bronchoalveolar lavage lymphocytes in patients with HIV infection.
Am Rev Respir Dis138:
1609–1615,
1988.
2.
BrodieSJMarcomKAPearsonLDAndersonBCde la Concha-BermejilloAEllisJADeMartiniJC:
Effects of virus load in the pathogenesis of lentivirus-induced lymphoid interstitial pneumonia.
J Infect Dis166:
531–541,
1992.
3.
ChassagneJVerrellePDionetCClavelFBarre-SinoussiFChermannJCMontagnierLGluckmanJCKlatzmannD:
A monoclonal antibody against LAV gag precursor: use for viral protein analysis and antigenic expression in infected cells.
J Immunol136:
1442–1445,
1986.
4.
CowardJEHarterDHMorganC:
Electron microscopic observations of visna virus-infected cell cultures.
Virology40:
1030–1038,
1970.
5.
CutlipRCLairdGA:
Isolation and characterization of a virus associated with progressive pneumonia (maedi) of sheep.
Am J Vet Res37:
1377–1382,
1976.
6.
CutlipRCLehmkuhlHDWoodRLBrodgenKA:
Arthritis associated with ovine progressive pneumonia.
Am J Vet Res46:
65–68,
1985.
7.
DalzielRGHopkinsJWattNJDuliaBMClarkeHAKMcConnellI:
Identification of a putative cellular receptor for the lentivirus visna virus.
J Gen Virol72:
1905–1911,
1991.
8.
DeMartiniJCBrodieSJde la Concha-BermejilloAEllisJALairmoreMD:
Pathogenesis of lymphoid interstitial pneumonia in natural and experimental ovine lentivirus infection.
Clin Infect Dis17
(Suppl 1):
236–242,
1993.
9.
DeMartiniJCMacHughNDNaessensJTealeAJ:
Differential in vitro and in vivo expression of MHC class II antigens in bovine lymphocytes infected by Theileria parva.
Vet Immunol Immunopathol35:
253–273,
1993.
10.
GendelmanHENarayanOMolineauxSClementsJEGhotbiZ:
Slow persistent replication of lentiviruses: role of tissue macrophages and macrophage-precursors in bone marrow.
Proc Natl Acad Sci USA82:
7086–7090,
1985.
11.
GeorgssonGHouwersDJPálssonPAPéturssonG:
Expression of viral antigens in the central nervous system of visna-infected sheep: an immunohistochemical study on experimental visna induced by virus strains of increased neurovirulence.
Acta Neuropathol (Berl)77:
299–306,
1989.
12.
GeorgssonGPálssonPA:
The histopathology of maedi: a slow, viral pneumonia of sheep.
Vet Pathol8:
63–80,
1971.
13.
GeorgssonGPálssonPAPanitchHNathansonNPéturssonG:
The ultrastructure of early visna lesions.
Acta Neuropathol (Berl)37:
127–135,
1977.
14.
GonzálezC:
Immunobiology of sheep macrophages.
MPh Thesis. University of Edinburgh, Edinburgh, Scotland,
1989.
15.
GorrellMDBrandonMRShefferDAdamsRJNarayanO:
Ovine lentivirus is macrophagetropic and does not replicate productively in T lymphocytes.
J Virol66:
2679–2688,
1992.
16.
GudnadóttirM:
Visna-maedi in sheep.
Prog Med Virol18:
336–349,
1974.
17.
HopkinsJMcConnellI.DalzielRGDutiaB:
Patterns of major histocompatibility complex class II expression by T cell subsets in different immunological compartments. 2. Altered expression and cell function following activation in vivo.
Eur J Immunol23:
2889–2896,
1993.
18.
JensenBNLisseIMGerstoftJBorgeskovSSkinh⊘jP:
Cellular profiles in bronchoalveolar lavage fluid of HIV-infected patients with pulmonary symptoms: relation diagnosis and prognosis.
AIDS (Lond)5:
527–533,
1991.
19.
KennedyPGENarayanOGhotbiZHopkinsJGendelmanHClementsJE:
Persitent expression of la antigen and viral genome in visna-maedi virus induced inflammatory cells. Possible role of lentivirus induced interferon.
J Exp Med162:
1970–1982,
1985.
20.
LairmoreMDAkitaGYRussellHIDeMartiniJC:
Replication and cytopathic effects of ovine lentivirus strains in alveolar macrophages correlate with in vivo pathogenicity.
J Virol61:
4038–4042,
1987.
21.
LujánLBegaraICollieDDSWattNJ:
Phenotypic analysis of cells in bronchoalveolar lavage fluid and peripheral blood of maedi visna infected sheep.
Clin Exp Immunol91:
272–276,
1993.
22.
LujánLGarcía MarínJFFernández de LucoDVargasMABadiolaJJ:
Pathological changes in the lungs and mammary glands of sheep and their relationship with maedi-visna infection.
Vet Rec129:
51–54,
1991.
23.
MackayCRBeyaMFMatzingerP:
γ/δ T cells express a unique surface molecule appearing late during thymic development.
Eur J Immunol19:
1477–1483,
1989.
24.
MackayCRHeinWRBrownMHMatzingerP:
Unusual expression of CD2 in sheep: implications for T cell interactions.
Eur J Immunol18:
1681–1688,
1988.
25.
MaddoxJFMackayCRBrandonMR:
Surface antigens, SBU-T4 and SBU-T8, of sheep T lymphocyte subsets defined by monoclonal antibodies.
Immunology55:
739–748,
1985.
26.
NarayanOClementsJE:
Biology and pathogenesis of lentiviruses.
J Gen Virol70:
1617–1639,
1989.
27.
NarayanOCorkLC:
Lentiviral disease of sheep and goats: chronic pneumonia, leukoencephalomyelitis and arthritis.
Rev Infect Dis7:
89–98,
1985.
28.
NarayanOShefferDClementsJETennekoonG:
Restricted replication of lentiviruses. Visna viruses induce a unique interferon during interaction between lymphocytes and infected macrophages.
J Exp Med162:
1954–1969,
1985.
29.
NarayanOWolinskyJSClementsJEStrandbergJDGriffinDECorkLC:
Slow virus replication: the role of macrophages in the persistence and expression of visna viruses of sheep and goats.
J Gen Virol59:
345–356,
1982.
30.
NarayanOZinkMC:
Role of macrophages in lentivirus infections.
Adv Vet Sci Comp Med32:
129–148,
1988.
31.
NathansonNPanitchHPálssonPAPéturssonGGeorgssonG:
Pathogenesis of visna. II. Effects of immunosuppression upon early central nervous system lesions.
Lab Invest35:
444–451,
1976.
32.
PelusoRHaaseAStowringLEdwardsMVenturaP:
A Trojan horse mechanism for the spread of visna virus in monocytes.
Virology147:
231–236,
1985.
33.
PépinMCannellaDFontaineJJPittetJCLe PapeA:
Ovine mononuclear phagocytes in situ: identification by monoclonal antibodies and involvement in experimental pyogranulomas.
J Leukoc Biol51:
188–198,
1992.
34.
PéturssonGAndrésdóttirVAndréssonÓTorsteinsdóttirSGeorgssonGPálssonPA:
Human and ovine lentiviral infections compared.
Comp Immunol Microbiol Infect Dis14:
277–287,
1991.
35.
PéturssonGNathansonNGeorgssonGPanitchHPálssonPA:
Pathogenesis of visna. I. Sequential virologic, serologic and pathologic studies.
Lab Invest35:
402–412,
1976.
36.
PlataFAutranBMartinsLPWain-HobsonSRaphaèlMMayaudCDenisMGuillonJMDebréP:
AIDS virus-specific cytotoxic T lymphocytes in lung disorders.
Nature328:
348–351,
1987.
37.
PyperJMClementsJEGondaMANarayanO:
Sequence homology between cloned capine arthritis encephalitis virus and visna virus, two neurotropic lentiviruses.
J Virol58:
665–670,
1986.
38.
ReyburnHTRoyDJBlacklawsBASarganDRMcConnellI:
Expression of maedi-visna virus major core protein, p25: development of a sensitive p25 antigen detection assay.
J Virol Methods37:
305–320,
1992.
39.
RoyDJWattNJIngmanTHouwersDJSarganDRMcConnellI:
A simplified method for the detection of maedi-visna virus RNA by in situ hybridization.
J Virol Methods36:
1–11,
1992.
40.
ScottPCChoiCLBrandonMR:
Genetic organization of the ovine MHC class II region.
Immunogenetics25:
116–122,
1987.
41.
SigurdssonB:
Maedi, a slow progressive pneumonia of sheep: an epizoological and a pathological study.
Br Vet J110:
225–270,
1954.
42.
SigurdssonBPálssonPA:
Visna of sheep. A slow, demyelinating infection.
Br J Exp Pathol39:
519–528,
1958.
43.
SigurdssonBThormarHPálssonPA:
Cultivation of visna virus in tissue culture.
Arch Gesamte Virusforsch10:
368–381,
1960.
44.
SonigoPAlizonMStaskusKKlatzmannDColeSDanosORetzelETiollaisPHaaseAWain-HobsonS:
Nucleotide sequence of the visna lentivirus: relationship to the AIDS-virus.
Cell42:
369–382,
1985.
45.
StaskusKACouchLBittermanPRetzelEFZupancicMListJHaaseAT:
In situ amplification of visna virus DNA in tissue sections reveals a reservoir of latently infected cells.
Microb Pathog11:
67–76,
1991.
46.
StowringLHaaseATPéturssonGGeorgssonGPálssonPLutleyRRoosRSzuchetS:
Detection of visna virus antigens and RNA in glial cells in foci of demyelination.
Virology141:
311–318,
1985.
47.
TakemotoKKMatternCFTStoneLBCoeJELavelleG:
Antigenic and morphological similarities of progressive pneumonia virus, a recently isolated “slow virus” of sheep, to visna and maedi viruses.
J Virol7:
301–308,
1971.
48.
TorsteinsdóttirSGeorgssonGGísladóttirERafnarBPálssonPAPéturssonG:
Pathogenesis of central nervous system lesions in visna: cell-mediated immunity and lymphocyte subsets in blood, brain and cerebrospinal fluid.
J Neuroimmunol41:
149–158,
1992.
49.
Van der MolenEJHouwersDJ:
Indurative lymphocytic mastitis in sheep after experimenial infection with maedi-visna virus.
Vet Q9:
193–202,
1987.
50.
WattNJKingTJCollieDMcIntyreNSarganDMcConnellI:
Clinicopathological investigation of primary, uncomplicated maedi-visna virus infection.
Vet Rec131:
455–461,
1992.
51.
WattNJMcIntyreNCollieDSarganDMcConnellI:
Phenotypic analysis of lymphocyte populations in the lungs and regional lymphoid tissue of sheep naturally infected with maedi visna virus.
Clin Exp Immunol90:
204–208,
1992.
52.
WinwardLDLeendertsenLShenDT:
Microimmunodiffusion test for diagnosis of ovine progressive pneumonia.
Am J Vet Res40:
564–566,
1979.
