Oropharyngeal Shedding of Gammaherpesvirus DNA by Cats, and Natural Infection of Salivary Epithelium

Abstract

Felis catus gammaherpesvirus-1 (FcaGHV1), a novel candidate oncogenic virus, infects cats worldwide. Whether the oropharynx is a site of virus shedding and persistence, and whether oronasal carcinomas harbor FcaGHV1 nucleic acid were investigated. In a prospective molecular epidemiological study, FcaGHV1 DNA was detected by cPCR in oropharyngeal swabs from 26/155 (16.8%) of cats. Oropharyngeal shedding was less frequently detected in kittens ≤3 months of age (5/94, 5.3%) than in older animals; >3 months to ≤1 year: 8/26, 30.8%, (p = 0.001, OR 7.91, 95% CI (2.320, 26.979)); >1 year to ≤6 years: 10/20, 50%, (p < 0.001, OR 17.8 95% CI (5.065, 62.557)); >6 years: 3/15, 33% (p = 0.078). Provenance (shelter-owned/privately owned) was not associated with shedding. In situ hybridization (ISH) identified FcaGHV1-infected cells in salivary glandular epithelium but not in other oronasal tissues from two of three cats shedding viral DNA in the oropharynx. In a retrospective dataset of 11 oronasopharyngeal carcinomas, a single tumor tested positive for FcaGHV1 DNA by ISH, a papillary carcinoma, where scattered neoplastic cells showed discrete nuclear hybridization. These data support the oronasopharynx as a site of FcaGHV1 shedding, particularly after maternal antibodies are expected to decline. The salivary epithelium is identified as a potential site of FcaGHV1 persistence. No evidence supporting a role for FcaGHV1 in feline oronasal carcinomas was found in the examined tumours.

Detection of Felis catus Gammaherpesvirus 1 in Domestic Cat Saliva: Prevalence, Risk Factors, and Attempted Virus Isolation

“…Our current study sought to build on this finding by examining, for the first time, the prevalence and quantity (viral load) of FcaGHV1 DNA in liquid saliva collected from cats. We found that 19.8% of domestic cats had detectable FcaGHV1 DNA shed in saliva, while Rose et al found a similar prevalence of 16.8% FcaGHV1 DNA-positive oropharyngeal swabs [ 22 ]. Together, these studies suggest that cats commonly shed FcaGHV1 via the oropharynx into saliva.…”

“…While numerous previous studies have characterized FcaGHV1 DNA prevalence in the blood (reviewed in [ 25 ]), a recent study by Rose et al [ 22 ] was the first to detect FcaGHV1 DNA shedding in the oral cavity. Our current study sought to build on this finding by examining, for the first time, the prevalence and quantity (viral load) of FcaGHV1 DNA in liquid saliva collected from cats.…”

“…Studies including a larger number of older animals and/or a larger number of very young animals may have a different outcome. For instance, Rose et al found that cats < 3 months old had a lower frequency of oropharyngeal shedding than older cats [ 22 ]. In this study, we found that feral cats had higher saliva viral load than non-feral cats.…”

“…With regard to host tissue and cellular tropism, FcaGHV1 has been found to infect a range of tissues [ 18 ] and, in blood, infects both B and T cells, a relatively unusual characteristic as GHVs typically have specific tropism for one or the other [ 20 ]. Notably, FcaGHV1 DNA and/or viral transcripts have been identified in tumor tissue from several cats suffering from neoplasia [ 21 , 22 , 23 , 24 ], but thus far, no clear link between FcaGHV1 and specific cancers has been established [ 25 ]. Studies have identified several risk factors for FcaGHV1 DNAemia in blood, including most notably male sex, older age, poor health condition, infection with feline immunodeficiency virus (FIV), and infection with hemotropic mycoplasma [ 10 , 12 , 13 , 17 , 18 ].…”

“…Likewise, many animal herpesviruses can be shed and transmitted via saliva [ 31 , 32 , 33 , 34 ], including feline herpesvirus type-1, an alphaherpesvirus of cats [ 35 ]. Recently, Rose et al [ 22 ] detected FcaGHV1 DNA in oropharyngeal swabs and salivary gland epithelial tissue of cats, suggesting salivary shedding of the virus as a potential mechanism of transmission. While these findings provide strong evidence for salivary shedding, the prevalence and risk factors of FcaGHV1 shedding in feline saliva have not been well characterized.…”