Mucosal Immune Response to Feline Enteric Coronavirus Infection

Abstract

Feline infectious peritonitis is a devastating, fatal disease of domestic cats caused by a pathogenic mutant virus derived from the ubiquitous feline enteric coronavirus (FECV). Infection by FECV is generally subclinical, and little is known about the mucosal immune response that controls and eliminates the virus. We investigated the mucosal immune response against FECV in an endemically infected breeding colony over a seven-month period. Thirty-three cats were grouped according to FECV seropositivity and fecal virus shedding into naïve/immunologically quiescent, convalescent and actively infected groups. Blood, fecal samples and colon biopsies were collected to assess the mucosal and systemic immunologic and virologic profile. Results showed that cats with active FECV infections have strong systemic IgG and mucosal IgA responses that wane after virus clearance. Significant FECV-specific mucosal T cell IFNγ responses were not detected in any of the three groups. A shift toward an inflammatory state in the mucosa was suggested by increased IL17:FoxP3 expression. However, no histologic abnormalities were observed, and no shifts in lymphocyte subpopulation phenotype or proliferation were noted. Together, the results suggest that control of FECV is mediated by humoral mucosal and systemic responses and that perturbations in the primary reservoir organ (colon) are minimal.

Feline Infectious Peritonitis Virus Nsp5 Inhibits Type I Interferon Production by Cleaving NEMO at Multiple Sites

“…To date, the control of FECV replication (which is the source of FIPV-causing mutant virus [45]) and the development of anti-coronavirus drugs [5,23,46] are two major preventive and therapeutic measures of FIPV. Since the coronavirus nsp5-encoded 3C-like protease (3CLpro) plays an important role in virus replication and immune evasion, 3CLpro is considered an attractive target for the development of anti-coronaviral therapeutics.…”

High-throughput viral microneutralization method for feline coronavirus using image cytometry

“…Cats were cared for in accordance with the Association for the Assessment of Laboratory Animal Care standards and with approval from the Colorado State University Institutional Animal Care and Use Committee (protocol 16-6390A, approved 11 July, 2017). EDTA plasma of the type I FECV-infected cats was collected and stored at −80 °C as part of a previous study in which cats were monitored monthly for plasma FCoV antibodies and fecal FCoV RNA over seven months ( Pearson et al, 2019 ). Five representative feline plasma samples ( Table 1 ) were vortexed, centrifuged, and heat-inactivated at 57 °C for 1 h ( Pearson et al, 2019 ).…”

“…EDTA plasma of the type I FECV-infected cats was collected and stored at −80 °C as part of a previous study in which cats were monitored monthly for plasma FCoV antibodies and fecal FCoV RNA over seven months ( Pearson et al, 2019 ). Five representative feline plasma samples ( Table 1 ) were vortexed, centrifuged, and heat-inactivated at 57 °C for 1 h ( Pearson et al, 2019 ). Next, 8 serial dilutions in DPBS were prepared directly in a 96-well titration plate (650201, Greiner Bio-One).…”

“…The complexity of the virus itself along with the variability of the clinical manifestation has confounded efforts to determine immune correlates of protection that should be targeted with vaccine strategies. We recently reported that control of FECV replication in naturally infected cats was associated with mucosal and systemic antibody responses while cell-mediated responses were minimally apparent ( Pearson et al, 2019 ). Therefore, assays to determine effector functions of antibodies will be crucial for the development and evaluation of a successful vaccine.…”

Dynamics of indicators of cellular immunity in conditions of acute generalized peritonitis in rats

“…The severity of peritonitis depends on the adequacy of the immune response. Correct immune response and sufficient reserves of compensation of the body contribute to the localization of the inflammation [6]. Immune deficiency causes an adverse course of peritonitis.…”