Postnatal persistent infection with classical Swine Fever virus and its immunological implications.
It is well established that trans-placental transmission of classical swine fever virus (CSFV) during mid-gestation can lead to persistently infected offspring. The aim of the present study was to evaluate the ability of CSFV to induce viral persistence upon early postnatal infection. Two litters of 10 piglets each were infected intranasally on the day of birth with low and moderate virulence CSFV isolates, respectively. During six weeks after postnatal infection, most of the piglets remained clinically healthy, despite persistent high virus titres in the serum. Importantly, these animals were unable to mount any detectable humoral and cellular immune response. At necropsy, the most prominent gross pathological lesion was a severe thymus atrophy. Four weeks after infection, PBMCs from the persistently infected seronegative piglets were unresponsive to both, specific CSFV and non-specific PHA stimulation in terms of IFN-γ-producing cells. These results suggested the development of a state of immunosuppression in these postnatally persistently infected pigs. However, IL-10 was undetectable in the sera of the persistently infected animals. Interestingly, CSFV-stimulated PBMCs from the persistently infected piglets produced IL-10. Nevertheless, despite the addition of the anti-IL-10 antibody in the PBMC culture from persistently infected piglets, the response of the IFN-γ producing cells was not restored. Therefore, other factors than IL-10 may be involved in the general suppression of the T-cell responses upon CSFV and mitogen activation. Interestingly, bone marrow immature granulocytes were increased and targeted by the virus in persistently infected piglets. Taken together, we provided the first data demonstrating the feasibility of CSFV in generating a postnatal persistent disease, which has not been shown for other members of the Pestivirus genus yet. Since serological methods are routinely used in CSFV surveillance, persistently infected pigs might go unnoticed. In addition to the epidemiological and economic significance of persistent CSFV infection, this model could be useful for understanding the mechanisms of viral persistence.
Centre de Recerca en Sanitat Animal (CReSA), IRTA-Universitat Autònoma de Barcelona (UAB), Campus de la UAB, Bellaterra, Barcelona, Spain.
Sara
S
Muñoz-González
Institute of Virology and immunology (IVI), Mittelhäusern, Switzerland.
Nicolas
N
Ruggli
Centre de Recerca en Sanitat Animal (CReSA), IRTA-Universitat Autònoma de Barcelona (UAB), Campus de la UAB, Bellaterra, Barcelona, Spain; Departament d'Agricultura, Ramaderia, Pesca, Alimentació i Medi Natural, (DAAM), Generalitat de Catalunya, Spain.
Rosa
R
Rosell
Centro Nacional de Sanidad Agropecuaria (CENSA), La Habana, Cuba.
Lester Josué
LJ
Pérez
Centro Nacional de Sanidad Agropecuaria (CENSA), La Habana, Cuba.
Maria Teresa
MT
Frías-Leuporeau
Departament de Producció Animal, ETSEA, Universidad de Lleida, Lleida, Spain.
Lorenzo
L
Fraile
Centre de Recerca en Sanitat Animal (CReSA), IRTA-Universitat Autònoma de Barcelona (UAB), Campus de la UAB, Bellaterra, Barcelona, Spain; Institut de Recerca i Tecnologia Agroalimentaria (IRTA), Barcelona, Spain.
Maria
M
Montoya
Centre de Recerca en Sanitat Animal (CReSA), IRTA-Universitat Autònoma de Barcelona (UAB), Campus de la UAB, Bellaterra, Barcelona, Spain.
Lorena
L
Cordoba
Centre de Recerca en Sanitat Animal (CReSA), IRTA-Universitat Autònoma de Barcelona (UAB), Campus de la UAB, Bellaterra, Barcelona, Spain; Departamento de Sanitat i d'Anatomia Animals, Facultat de Veterinària, UAB, Bellaterra-Barcelona, Spain.
Mariano
M
Domingo
Institute of Veterinary Pathology, Division of Immunopathology, University Zürich, Zürich, Switzerland.
Felix
F
Ehrensperger
Institute of Virology and immunology (IVI), Mittelhäusern, Switzerland.
Artur
A
Summerfield
Centre de Recerca en Sanitat Animal (CReSA), IRTA-Universitat Autònoma de Barcelona (UAB), Campus de la UAB, Bellaterra, Barcelona, Spain.
Llilianne
L
Ganges
D000818:Animals; D000831:Animals, Newborn; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D006691:Classical Swine Fever / Q000276:immunology* / Q000821:virology*; D006692:Classical Swine Fever Virus / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D005260:Female; D006098:Granulocytes / Q000276:immunology / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000276:immunology*; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood; D016753:Interleukin-10 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D013552:Swine; D019562:Viral Load
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D016753:Interleukin-10; D007371:Interferon-gamma