Viral infections and their ability to dysregulate the immune system.

In John Butler’s laboratory the focus of study is development of the fetal and neonatal piglet’s adaptive immune repertoire. Previously, our laboratory has examined the effects of gastrointestinal colonization with commensal and pathogenic strains of bacteria on the humoral immune system, e.g. the repertoire of tissue-localized and systemic B-cells and their responsiveness to immunization in terms of antibody production. However, the effect of a viral infection on the developing humoral system of neonatal isolator piglets had not been explored. Porcine reproductive and respiratory syndrome virus (PRRSV) is currently considered the most important swine pathogen worldwide. As the name suggests, infection with this virus induces reproductive failure in sows and respiratory disease, especially in young piglets. I chose to study the impact of this virus on the neonatal piglet’s humoral immune system because of its relevance to the laboratory’s previous work and its significance as a swine pathogen. The main goals of my thesis project have been: (1) to understand how PRRSV infection impacts the neonatal piglet’s developing humoral immune system, (2) to determine whether PRRSV infection causes modulation of antigen-specific antibody responses, (3) to elucidate the effect of PRRSV infection on immunoglobulin VH gene usage in B-cells, and (4) to begin to understand the mechanism(s) by which the PRRSV brings about its effects on the immune system. I have found that PRRSV infection leads to a dysregulation of the neonate’s humoral immune system, a modulation/suppression of antigen-specific antibody responses, and an overwhelming polyclonal B-cell activation.

Butler JE, Lemke CD, Weber P, Sinkora M, Lager KM. Antibody repertoire development in fetal and neonatal piglets: XIX. Undiversified B cells with hydrophobic HCDR3s preferentially proliferate in the porcine reproductive and respiratory syndrome. J Immunol. 2007 May 15;178(10):6320-31. PubMed PMID:17475861.

Butler JE, Sinkora M, Wertz N, Holtmeier W, Lemke CD. Development of the neonatal B and T cell repertoire in swine: implications for comparative and veterinary immunology. Vet Res. 2006 May-Jun;37(3):417-41. Epub 2006 Mar 9. Review. PubMed PMID: 16611556.

Butler JE, Wertz N, Sun J, Wang H, Lemke C, Chardon P, Piumi F, Wells K. The pre-immune variable kappa repertoire of swine is selectively generated from certain subfamilies of Vkappa2 and one Jkappa gene. Vet Immunol Immunopathol. 2005 Oct 18;108(1-2):127-37. PubMed PMID: 16112743.