Characterization of antiviral T cell responses during primary and secondary challenge of laboratory cats with feline infectious peritonitis virus (FIPV)

Abstract

Background Feline infectious peritonitis (FIP) is considered highly fatal in its naturally occurring form, although up to 36% of cats resist disease after experimental infection, suggesting that cats in nature may also resist development of FIP in the face of infection with FIP virus (FIPV). Previous experimental FIPV infection studies suggested a role for cell-mediated immunity in resistance to development of FIP. This experimental FIPV infection study in specific pathogen free (SPF) kittens describes longitudinal antiviral T cell responses and clinical outcomes ranging from rapid progression, slow progression, and resistance to disease. Results Differences in disease outcome provided an opportunity to investigate the role of T cell immunity to FIP determined by T cell subset proliferation after stimulation with different viral antigens. Reduced total white blood cell (WBC), lymphocyte and T cell counts in blood were observed during primary acute infection for all experimental groups including cats that survived without clinical FIP. Antiviral T cell responses during early primary infection were also similar between cats that developed FIP and cats remaining healthy. Recovery of antiviral T cell responses during the later phase of acute infection was observed in a subset of cats that survived longer or resisted disease compared to cats showing rapid disease progression. More robust T cell responses at terminal time points were observed in lymph nodes compared to blood in cats that developed FIP. Cats that survived primary infection were challenged a second time to pathogenic FIPV and tested for antiviral T cell responses over a four week period. Nine of ten rechallenged cats did not develop FIP or T cell depletion and all cats demonstrated antiviral T cell responses at multiple time points after rechallenge. Conclusions In summary, definitive adaptive T cell responses predictive of disease outcome were not detected during the early phase of primary FIPV infection. However emergence of antiviral T cell responses after a second exposure to FIPV, implicated cellular immunity in the control of FIPV infection and disease progression. Virus host interactions during very early stages of FIPV infection warrant further investigation to elucidate host resistance to FIP.

The Effect of Natural Feline Coronavirus Infection on the Host Immune Response: A Whole-Transcriptome Analysis of the Mesenteric Lymph Nodes in Cats with and without Feline Infectious Peritonitis

“…When genes from the categories T cell differentiation and T cell mediated immunity were analysed separately, T cell features were relatively lower in FIP cats than either group of cats without FIP. Consistent with this, anti-viral T cell responses (as determined by proliferation assays and T cell subsets) were found to be higher in cats resistant to experimental FIP in a recent study [62]. This supports a deficiency in cats that succumb to the disease, either at the level of initial detection (cell surface receptor signaling) or in sustaining an appropriate response.…”

Mucosal Immune Response to Feline Enteric Coronavirus Infection

“…It has been hypothesized that a failed T cell response distinguishes between disease resistance and progressive FIP [35,36,37,38]. This was been carefully investigated in a recent study that characterized T cell responses in cats with primary FIPV infection and in survivors of the primary infection that received a secondary challenge with the same virus [39]. T cell responses were not apparent during the acute phase of primary infection, but they did emerge during the secondary infection and were correlated with protection against FIPV progression.…”

Older adults lack SARS CoV-2 cross-reactive T lymphocytes directed to human coronaviruses OC43 and NL63

“…The supernatant was harvested on day seven post-infection and subjected to concentration by ultracentrifugation using a 20% sucrose cushion. The concentrated virus was then inactivated using a proprietary inactivation method based on binary ethylenimine (European Veterinary Laboratory (EVL, Netherlands) 50 , 51 . A clinical isolate of RSV (RSV-A-0594; kindly provided by Thomas Schulz; Institute of Virology Hannover Medical School) was grown in HEp-2 cells in Opti-MEM (Thermo Fisher Scientific) and titrated using a modified immunoplaque assay as described previously 52 .…”