Antigen-Specific B-Cell Responses to Porcine Reproductive and Respiratory Syndrome Virus Infection

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) causes an acute, viremic infection of 4 to 6 weeks, followed by a persistent infection lasting for several months. We characterized antibody and B-cell responses to viral proteins in acute and persistent infection to better understand the immunological basis of the prolonged infection. The humoral immune response to PRRSV was robust overall and varied among individual viral proteins, with the important exception of a delayed and relatively weak response to envelope glycoprotein 5 (GP5). Memory B cells were in secondary lymphoid organs, not in bone marrow or Peyer's patches, in contrast to the case for many mammalian species. Potent anti-PRRSV memory responses were elicited to recall antigen in vitro, even though a second infection did not increase the B-cell response in vivo, suggesting that productive reinfection does not occur in vivo. Antibody titers to several viral proteins decline over time, even though abundant antigen is known to be present in lymphoid tissues, possibly indicating ineffective antigen presentation. The appearance of antibodies to GP5 is delayed relative to the resolution of viremia, suggesting that anti-GP5 antibodies are not crucial for resolving viremia. Lastly, viral infection had no immunosuppressive effect on the humoral response to a second, unrelated antigen. Taking these data together, the active effector and memory B-cell responses to PRRSV are robust, and over time the humoral immune response to PRRSV is effective. However, the delayed response against GP5 early in infection may contribute to the prolonged acute infection and the establishment of persistence.

Broadly neutralizing antibodies against the rapidly evolving porcine reproductive and respiratory syndrome virus

“…Factors such as extensive viral genetic and antigenic diversity, large populations of animals in regions of dense swine production that facilitate spread of virus, persistence of virus for extended periods in pigs during which it can be transmitted to susceptible animals, and inability of current vaccines to prevent infection in populations all contribute to the problem of PRRSV spread and persistence. Pigs generate a well-documented humoral immune response against PRRSV (Molina et al, 2008;Mulupuri et al, 2008;Nelson et al, 1994). However the slow kinetics, small magnitude and limited breadth of protection observed from the neutralizing antibody response have led to the belief that it is not an important factor, nor realistic approach, for achieving widespread protection against PRRSV (reviewed in Darwich et al, 2010;Murtaugh and Genzow, 2011).…”

Antibody Response to Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Nonstructural Proteins and Implications for Diagnostic Detection and Differentiation of PRRSV Types I and II

“…Previous studies of the humoral immune response to PRRSV focused mainly on detection of antibodies to viral structural proteins, especially N (9,22,26,29). Several studies showed that certain nsps, such as nsp1 and nsp2, are highly immunogenic (4,7,13,24,25).…”

GP5 expression in Marc-145 cells inhibits porcine reproductive and respiratory syndrome virus infection by inducing beta interferon activity

“…Immunization with exogenous GP5 or encoding GP5 plasmids (Lopez and Osorio, 2004;Pirzadeh and Dea, 1998) has been shown to induce neutralizing antibodies. However, the neutralizing antibodies against GP5 in pigs infected with PRRSV were delayed approximately 2 weeks compared with antibodies to N and Nsp2 (Mulupuri et al, 2008) suggesting that the neutralization antibody inducing function of GP5 was modulated by the other PRRSV proteins during PRRSV infection. This indicates that expressing GP5 in PRRSV a susceptible cell before virus infection is a preferable method to investigate the role of GP5 in PRRSV infection.…”

“…Immunization with exogenous GP5 or exposure to native GP5 by means of DNA immunization can provide some degree of immune protection to PRRSV infection in pigs (Lopez and Osorio, 2004). However, in PRRSV infected pigs, the production of antibodies against GP5 is delayed by approximately 2 weeks compared with the antibodies to N and Nsp2 (Mulupuri et al, 2008).…”