Interferon in Nasal Secretions and Sera of Calves After Intranasal Administration of Avirulent Infectious Bovine Rhinotracheitis Virus: Association of Interferon in Nasal Secretions with Early Resistance to Challenge with Virulent Virus

Abstract

Calves which had received avirulent infectious bovine rhinotracheitis virus (AV-IBR) by intranasal (IN) administration developed detectable levels of interferon (IF) in nasal secretions as early as 40 hr later. Peak titers (1:640) of IF appeared in secretions 72 to 96 hr after administration of virus, and titers of 1:80 to 1:320 were maintained through the 8th day. Lower titers (1:5 to 1:10) of IF were detected in sera obtained on the 4th to 8th days after administration of virus. Peak titers of IF in respiratory tract secretions were accompanied by a 100to > 1,000fold reduction in the levels of AV-IBR present in the secretions. Serum antibody was not detected prior to the 8th day after administration of AV-IBR. Calves which received AV-IBR by the IN route 72 or 96 hr earlier were refractory to challenge with virulent infectious bovine rhinotracheitis virus (IBR), whereas calves receiving AV-IBR 18 or 40 hr earlier became clinically ill following challenge. The temporal association between appearance of IF in respiratory tract secretions and onset of protection against challenge suggests a cause and effect relationship. No IF was detected in either nasal secretions or sera of calves receiving modified IBR virus by intramuscular injection. Following subsequent IN challenge of these calves, IF was detected in nasal secretions as early as 24 hr postchallenge and was maintained at titers of 1:40 to 1:80 for approximately 4 days, even in the absence of virus recovery. Greater ease of local IF induction with IBR virus in calves previously sensitized with that virus is suggested.The elaboration of interferon (IF) by cells in response to virus infection is considered a major factor of the host defense mechanism, particularly during the course of primary infections. Studies related to induction, synthesis, properties, and mechanism of action of IF have been reviewed (3,4,11,21,35,37). Studies on the in vitro induction of IF by calf kidney cells infected with several different viruses and the in vivo induction of circulating IF in the bovine by viral and nonviral inducers have been reported (9,19,(29)(30)(31)(32)34). These studies have not provided information on the role of IF in either preventing or influencing the outcome of viral infections in the bovine.Investigations were undertaken in our laboratory to evaluate factors involved in early onset of protection against infectious bovine rhinotracheitis virus (IBR) challenge following intranasal (IN) administration of an avirulent strain of IBR (AV-IBR). It was discovered that high levels of IF developed in nasal secretions after AV-IBR administration and that the time of first appearance coincided with the time resistance to challenge with virulent virus became evident. Subsequent studies were conducted to evaluate the relationships between virus and IF levels in nasal secretions and sera of calves after IN or intramuscular 699 on July 6, 2020 by guest http://iai.asm.org/ Downloaded from

Bovine interferon: Its biology and application in veterinary medicine

“…Recently some variability in sensitivity of different BHV-1 strains was observed but none of them were nearly as sensitive as was VSV [49]. These findings corroborate the in vivo findings, where maximal IFN-titers in nasal secretion of BHV-1 challenged calves occur simultaneously with maximal virus-titers [20,75,113], and exogenous BolFN applied intranasally prior to nasal challenge with BHV-1 does not reduce replication to any significant degree, indicating the insensitivity of BHV-1 in vivo to the direct antiviral effects of BolFN [4,11]. Most other viruses, reputedly involved in respiratory disease in cattle, show moderate to high sensitivity to natural and recombinant BolFNs in vitro [4,49].…”

“…Numerous viruses have been reported to induce IFN in cattle. These include Newcastle disease virus, vaccinia virus, bovine parainfluenza-3 virus, bovine respiratory syncytial virus, bovine adenovirus, bovine enterovirus (strain LCR-4), BVDV, bovine herpesvirus-1 (BHV-1) (s. IBRV/IPV) and bovine rotaviruses [20,34,35,36,44,67,75,88,91,92,94,101,110,113,118,126]. However, the role of IFN in limiting virus replication has not been established for most of these infections with the exception of BHV-1.…”

“…However, the role of IFN in limiting virus replication has not been established for most of these infections with the exception of BHV-1. Several groups have found a clear relationship between replication of BHV-1 in the nasal passage and IFN-titers in nasal secretions [20,75,113]. In contrast, IFN levels in serum are usually negligible following a respiratory tract infection with BHV-1, even though BHV-1 is believed to produce systemic infections [20,113, and u~apublished data].…”

“…In contrast, IFN levels in serum are usually negligible following a respiratory tract infection with BHV-1, even though BHV-1 is believed to produce systemic infections [20,113, and u~apublished data]. Locally induced IFN, following an aerogenic BHV-1 infection, can confer at least partial protection against a secondary infection with either BHV-1 or an unrelated virus [34,35,36,110,113]. Whether locally produced IFN can have systemic effects and alter the outcome of the infection remains to be determined.…”

Neonatal Immune Development in the Calf and Its Impact on Vaccine Response

“…Maternal interference is less likely at mucosal sites in young animals, so most of them develop active immunity [41,58]. After IN vaccination, high levels of mucosal and serum interferon are also produced [63] that direct an antiviral effect and may aid in the development of the neonatal immune response. BHV-1 is also immunosuppressive [64].…”