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Use of unbiased metagenomic and transcriptomic analyses to investigate the association between feline calicivirus and feline chronic gingivostomatitis in domestic cats

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  • 1 Department of Biochemistry and Biophysics, School of Medicine, University of California-San Francisco, San Francisco, CA 94158.
  • | 2 Department of Biological Sciences, Dana and David Dornslife College of Letters, Arts, and Sciences, University of Southern California, Los Angeles, CA 90089.
  • | 3 VCA San Francisco Veterinary Specialists, San Francisco, CA 94110.
  • | 4 Aggie Animal Dental Center, Mill Valley, CA 94941.
  • | 5 Department of Surgical and Radiological Sciences and Veterinary Institute for Regenerative Cures, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616.
  • | 6 Chan-Zuckerberg Biohub, San Francisco, CA 94158.
  • | 7 Department of Oral Health Sciences, School of Dentistry, University of Washington, Seattle, WA 98195.
  • | 8 DentaQuest Impact Inc, Boston, MA 02129.

Abstract

OBJECTIVE

To identify associations between microbes and host genes in cats with feline chronic gingivostomatitis (FCGS), a debilitating inflammatory oral mucosal disease with no known cause, compared with healthy cats and cats with periodontitis (control cats).

ANIMALS

19 control cats and 23 cats with FCGS.

PROCEDURES

At least 1 caudal oral mucosal swab specimen was obtained from each cat. Each specimen underwent unbiased metatranscriptomic next-generation RNA sequencing (mNGS). Filtered mNGS reads were aligned to all known genetic sequences from all organisms and to the cat transcriptome. The relative abundances of microbial and host gene read alignments were compared between FCGS-affected cats and control cats and between FCGS-affected cats that did and did not clinically respond to primary treatment. Assembled feline calicivirus (FCV) genomes were compared with reverse transcription PCR (RT-PCR) primers commonly used to identify FCV.

RESULTS

The only microbe strongly associated with FCGS was FCV, which was detected in 21 of 23 FCGS-affected cats but no control cats. Problematic base pair mismatches were identified between the assembled FCV genomes and RT-PCR primers. Puma feline foamy virus was detected in 9 of 13 FCGS-affected cats that were refractory to treatment and 5 healthy cats but was not detected in FCGS-affected cats that responded to tooth extractions. The most differentially expressed genes in FCGS-affected cats were those associated with antiviral activity.

CONCLUSIONS AND CLINICAL RELEVANCE

Results suggested that FCGS pathogenesis has a viral component. Many FCV strains may yield false-negative results on RT-PCR-based assays. Coinfection of FCGS-affected cats with FCV and puma feline foamy virus may adversely affect response to treatment.

Abstract

OBJECTIVE

To identify associations between microbes and host genes in cats with feline chronic gingivostomatitis (FCGS), a debilitating inflammatory oral mucosal disease with no known cause, compared with healthy cats and cats with periodontitis (control cats).

ANIMALS

19 control cats and 23 cats with FCGS.

PROCEDURES

At least 1 caudal oral mucosal swab specimen was obtained from each cat. Each specimen underwent unbiased metatranscriptomic next-generation RNA sequencing (mNGS). Filtered mNGS reads were aligned to all known genetic sequences from all organisms and to the cat transcriptome. The relative abundances of microbial and host gene read alignments were compared between FCGS-affected cats and control cats and between FCGS-affected cats that did and did not clinically respond to primary treatment. Assembled feline calicivirus (FCV) genomes were compared with reverse transcription PCR (RT-PCR) primers commonly used to identify FCV.

RESULTS

The only microbe strongly associated with FCGS was FCV, which was detected in 21 of 23 FCGS-affected cats but no control cats. Problematic base pair mismatches were identified between the assembled FCV genomes and RT-PCR primers. Puma feline foamy virus was detected in 9 of 13 FCGS-affected cats that were refractory to treatment and 5 healthy cats but was not detected in FCGS-affected cats that responded to tooth extractions. The most differentially expressed genes in FCGS-affected cats were those associated with antiviral activity.

CONCLUSIONS AND CLINICAL RELEVANCE

Results suggested that FCGS pathogenesis has a viral component. Many FCV strains may yield false-negative results on RT-PCR-based assays. Coinfection of FCGS-affected cats with FCV and puma feline foamy virus may adversely affect response to treatment.

Supplementary Materials

    • Supplementary Figure S1 (PDF 256 KB)
    • Supplementary Figure S2 (PDF 1,665 KB)
    • Supplementary Figure S3 (PDF 1,246 KB)
    • Supplementary Figure S4 (PDF 205 KB)
    • Supplementary Figure S5 (PDF 978 KB)
    • Supplementary Figure S6 (PDF 1,770 KB)
    • Supplementary Table S1 (PDF 135 KB)
    • Supplementary Table S2 (PDF 93 KB)
    • Supplementary Table S3 (PDF 123 KB)

Contributor Notes

Dr. Soltero-Rivera's present address is VCA Bay Area Veterinary Specialists and Emergency Hospital, San Leandro, CA 94578.

Mr. Fried and Dr. Soltero-Rivera contributed equally to this work.

Address correspondence to Dr. Horst (jahorst@gmail.com).