Selective Lymphocyte Depletion during the Early Stage of the Immune Response to Foot-and-Mouth Disease Virus Infection in Swine

Abstract

Foot-and-mouth disease virus (FMDV) is the causative agent of a highly contagious vesicular disease of cloven-hoofed animals. In the present study we use FMDV serotype C infection of swine to determine, by analytical techniques, the direct ex vivo visualization of virus-infected immune cells during the first 17 days of infection. We report, for the first time, that FMDV C-S8c1 can infect T and B cells at short periods of time postinoculation, corresponding with the peak of the viremia. There is a significant lymphopenia that involves cells in lymph nodes and spleen is observed. This selective depletion of T cells is not due mainly to in situ death via apoptosis as visualized by the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) technique. Thus, early infection of T cells by FMDV may be the main cause of the observed T-cell depletion.Importantly, this lack of T cells is reflected in a reduced response to mitogen activation, which in many cases is totally eliminated. These data suggest a mechanism by which the virus causes a transient immunosuppression, subvert the immune systems, and spreads. These results have important implications for our understanding of early events in the development of a robust immune response against FMDV.

Comparative study of experimental Foot-and-Mouth Disease in cattle (Bos indicus) and buffaloes (Bubalis bubalus)

“…This is in agreement with the recent findings of experimental studies in pigs, mice and guinea pigs (Bautista et al 2003;Diaz-San Segundo et al 2006;Bartels et al 1994). However, studies on naturally infected animals indicated lymphocytosis and also unaltered leucocyte levels (Mohapatra et al 2005;Gokce et al 2004;Elitok et al 2005).…”

“…However, studies on naturally infected animals indicated lymphocytosis and also unaltered leucocyte levels (Mohapatra et al 2005;Gokce et al 2004;Elitok et al 2005). Earlier studies have associated the lymphopenia in FMDV infected animals with impaired function of residual T-cells with a transient immunosuppression (Bautista et al 2003;Diaz-San Segundo et al 2006;Ostrowski et al 2005;Parida et al 2006). This facilitates viral pathogenesis including systemic spread and viral shedding into environment to enable its transmission.…”

“…But experimental studies on FMD in Indian cattle (Bos indicus) and buffaloes (Bubalis bubalus) are rare (Gomes et al 1997). Furthermore, the leucocytic changes in the acute stage of disease are important in disease progression (Bautista et al 2003;Diaz-San Segundo et al 2006). However, previous study findings are divisive (Bautista et al 2003;Diaz-San Segundo et al 2006;Mohapatra et al 2005;Gokce et al 2004).…”

“…Furthermore, the leucocytic changes in the acute stage of disease are important in disease progression (Bautista et al 2003;Diaz-San Segundo et al 2006). However, previous study findings are divisive (Bautista et al 2003;Diaz-San Segundo et al 2006;Mohapatra et al 2005;Gokce et al 2004). The purpose of the present study is to compare clinical, leucocytic and pathological findings in cattle and buffalo experimentally infected with FMDV serotype Asia 1.…”

Inoculation of Swine with Foot-and-Mouth Disease SAP-Mutant Virus Induces Early Protection against Disease

“…A dynamic balance exists between pro-and antiinflammatory components (57) that could be disrupted upon viral infection. Previous studies have shown that during acute FMDV infection in swine, the virus induces an immunosuppressive stage, characterized by T cell unresponsiveness and transient lymphopenia affecting all T cell subsets and correlating with the appearance of viremia (3,26). One possible mechanism by which the virus induces immunosuppression might be related to the production of IL-10 (25), an immunosuppressive cytokine that plays an important stimulatory role in the function of B lymphocytes and the production of antibodies by B1 lymphocytes (2).…”