Absence of surface expression of feline infectious peritonitis virus (FIPV) antigens on infected cells isolated from cats with FIP

Cornelissen, Els; Dewerchin, Hannah L.; Hamme, Evelien Van; Nauwynck, Hans

doi:10.1016/j.vetmic.2006.11.026

Cited by 17 publications

(20 citation statements)

References 15 publications

(15 reference statements)

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“…So at least in terms of CD16-expression, peripheral NK cells from FIP cats seem to be better equipped for ADCC. Although the relative increase was significant, the five-fold reduction in absolute NK cell numbers seen earlier, in addition to the absence of viral proteins in 50% of FIPV-infected cells and the rapid internalization of cell-surface bound antibodies in infected cells, somewhat lowers the impact of this finding (Cornelissen et al, 2007;Dewerchin et al, 2008).…”

Section: Discussionmentioning

confidence: 71%

“…The current hypothesis states that FIPV arises through mutation from the avirulent coronavirus feline enteric coronavirus (FECV) (Chang et al, 2010). Additionally, FIPV is very immune evasive, especially toward the humoral branch of immunity (Pedersen and Boyle, 1980;Cornelissen et al, 2007;Dewerchin et al, 2008). About 30 years ago, Pedersen and Black (1983) already stated that a strong cell-mediated immune response (CMI) is key to surviving a FIPV infection.…”

Section: Introductionmentioning

confidence: 99%

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Suppression of NK cells and regulatory T lymphocytes in cats naturally infected with feline infectious peritonitis virus

Vermeulen

Devriendt

Olyslaegers

et al. 2013

Veterinary Microbiology

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A strong cell-mediated immunity (CMI) is thought to be indispensable for protection against infection with feline infectious peritonitis virus (FIPV) in cats. In this study, the role of natural killer (NK) cells and regulatory T cells (Tregs), central players in the innate and adaptive CMI respectively, was examined during natural FIPV infection. When quantified, both NK cells and Tregs were drastically depleted from the peripheral blood, mesenteric lymph node (LN) and spleen in FIP cats. In contrast, mesentery and kidney from FIP cats did not show any difference when compared to healthy non-infected control animals. In addition, other regulatory lymphocytes (CD4+CD25-Foxp3+ and CD3+CD8+Foxp3+) were found to be depleted from blood and LN as well. Phenotypic analysis of blood-derived NK cells in FIP cats revealed an upregulation of activation markers (CD16 and CD25) and migration markers (CD11b and CD62L) while LN-derived NK cells showed upregulation of only CD16 and CD62L. LN-derived NK cells from FIPV-infected cats were also significantly less cytotoxic when compared with healthy cats. This study reveals for the first time that FIPV infection is associated with severe suppression of NK cells and Tregs, which is reflected by cell depletion and lowered cell functionality (only NK cells). This will un-doubtfully lead to a reduced capacity of the innate immune system (NK cells) to battle FIPV infection and a decreased capacity (Tregs) to suppress the immunopathology typical for FIP. However, these results will also open possibilities for new therapies targeting specifically NK cells and Tregs to enhance their numbers and/or functionality during FIPV infection.

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Section: Discussionmentioning

confidence: 71%

Section: Introductionmentioning

confidence: 99%

Suppression of NK cells and regulatory T lymphocytes in cats naturally infected with feline infectious peritonitis virus

Vermeulen

Devriendt

Olyslaegers

et al. 2013

Veterinary Microbiology

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“…Even though only about 1 % of the monocytes was infected with FIPV, the fact that every infected monocyte was able to internalize its viral proteins adds to the likelihood that internalization occurs in vivo as well. In addition, we have found that FCoV-infected monocytes in naturally infected FIP cats show no membrane expression (Cornelissen et al, 2007). However, membrane expression returns after in vitro cultivation, which indicates that internalization might occur in vivo.…”

Section: Discussionmentioning

confidence: 88%

“…In previous work, we reported that the membranebound viral proteins, the spike and the membrane protein, are internalized upon antibody binding, which results in the loss of detectable viral proteins on the plasma membrane (Dewerchin et al, 2006). The fact that no surface-expressed viral antigens can be found on FCoVinfected monocytes isolated from naturally infected FIP cats, and that surface expression returns after isolation and in vitro cultivation of the monocytes, is the first indication that this immune-evasion strategy also exists in vivo (Cornelissen et al, 2007). If internalization could be blocked, then the humoral immune system would be able to contribute to the elimination of infected monocytes either by antibody-dependent complement-mediated or antibody-dependent cell-mediated lysis.…”

Section: Introductionmentioning

confidence: 99%

Surface-expressed viral proteins in feline infectious peritonitis virus-infected monocytes are internalized through a clathrin- and caveolae-independent pathway

Dewerchin

Cornelissen

Hamme

et al. 2008

Journal of General Virology

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Infection with feline infectious peritonitis virus (FIPV), a feline coronavirus, frequently leads to death in spite of a strong humoral immune response. In previous work, we reported that infected monocytes, the in vivo target cells of FIPV, express viral proteins in their plasma membranes. These proteins are quickly internalized upon binding of antibodies. As the cell surface is cleared from viral proteins, internalization might offer protection against antibody-dependent cell lysis. Here, the internalization and subsequent trafficking of the antigen-antibody complexes were characterized using biochemical, cell biological and genetic approaches. Internalization occurred through a clathrin-and caveolae-independent pathway that did not require dynamin, rafts, actin or rho-GTPases. These findings indicate that the viral antigen-antibody complexes were not internalized through any of the previously described pathways. Further characterization showed that this internalization process was independent from phosphatases and tyrosine kinases but did depend on serine/threonine kinases. After internalization, the viral antigen-antibody complexes passed through the early endosomes, where they resided only briefly, and accumulated in the late endosomes. Between 30 and 60 min after antibody addition, the complexes left the late endosomes but were not degraded in the lysosomes. This study reveals what is probably a new internalization pathway into primary monocytes, confirming once more the complexity of endocytic processes.

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“…Both processes result in the clearance of all detectable viral antigens from the plasma membrane of infected cells (Dewerchin et al, 2005;Dewerchin et al, 2006). FIPVinfected monocytes/macrophages isolated from naturally infected cats do not express viral proteins at their plasma membrane either (Cornelissen et al, 2007). Absence of viral proteins in the plasma membrane of infected monocytes can protect the infected cells from efficient ADCML.…”

mentioning

confidence: 99%

Absence of antibody-dependent, complement-mediated lysis of feline infectious peritonitis virus-infected cells

et al. 2009

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Cats infected with virulent feline coronavirus which causes feline infectious peritonitis (FIP) usually succumb to disease despite high antibody concentrations. One of the mechanisms that can help resolving infection is antibody-dependent, complement-mediated lysis (ADCML) of infected cells. ADCML consists of virus-specific antibodies that bind to cell surface expressed viral proteins which result in complement activation and cell lysis. The objective of this study was to determine the sensitivity of FIP-virus (FIPV) infected cells towards ADCML and to examine the role of the accessory proteins 3abc and 7ab in this process. ADCML assays, using FIPV strain 79-1146 and its deletion mutant strain Delta 3abc/Delta 7ab, were performed on: (i) CrFK cells that show surface-expressed viral antigens, (ii) monocytes without surface-expressed viral proteins due to retention and (iii) monocytes with surface-expressed viral proteins since the antibody-mediated internalization of these proteins was blocked. As expected, no ADCML was detected of the monocytes without surface-expressed viral antigens. Surprisingly, no lysis was observed in the CrFK cells and the monocytes that do show surface-expressed viral proteins, while controls showed that the ADCML assay was functional. These experiments proof that FIPV can employ another immune evasion strategy against ADCML (besides preventing surface expression): the inhibition of complement-mediated lysis. This new evasion strategy is not attributed to the group-specific proteins since lysis of cells infected with FIPV Delta 3abc/Delta 7ab was not detected.

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Absence of surface expression of feline infectious peritonitis virus (FIPV) antigens on infected cells isolated from cats with FIP

Cited by 17 publications

References 15 publications

Suppression of NK cells and regulatory T lymphocytes in cats naturally infected with feline infectious peritonitis virus

Suppression of NK cells and regulatory T lymphocytes in cats naturally infected with feline infectious peritonitis virus

Surface-expressed viral proteins in feline infectious peritonitis virus-infected monocytes are internalized through a clathrin- and caveolae-independent pathway

Absence of antibody-dependent, complement-mediated lysis of feline infectious peritonitis virus-infected cells

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