Infection with a Recently Discovered Gammaherpesvirus Variant in European Badgers, Meles meles, is Associated with Higher Relative Viral Loads in Blood

Abstract

Herpesviruses are ubiquitous pathogens infecting most animals. Although host immunity continually coevolves to combat virulence, viral variants with enhanced transmissibility or virulence occasionally emerge, resulting in disease burdens in host populations. Mustelid gammaherpesvirus 1 (MusGHV-1) is the only herpesvirus species identified thus far in European badgers, Meles meles. No MusGHV-1 associated pathomorbidity has been reported, but reactivation of MusGHV-1 in genital tracts is linked to impaired female reproductive success. An analysis of a short sequence from the highly conserved DNA polymerase (DNApol) gene previously identified two variants in a single host population. Here we compared genetic variance in blood samples from 66 known individuals of this same free-ranging badger population using a partial sequence comprising 2874 nucleotides of the DNApol gene, among which we identified 15 nucleotide differences resulting in 5 amino acid differences. Prevalence was 86% (59/66) for the common and 17% (11/66) for the novel variant, with 6% (4/66) of badgers presenting with coinfection. MusGHV-1 variants were distributed unevenly across the population, with individuals infected with the novel genotype clustered in 3 of 25 contiguous social groups. Individuals infected with the novel variant had significantly higher MusGHV-1 viral loads in their blood (p = 0.002) after adjusting for age (juveniles > adults, p < 0.001) and season (summer > spring and autumn, p = 0.005; mixed-effect linear regression), likely indicating higher virulence of the novel variant. Further genome-wide analyses of MusGHV-1 host resistance genes and host phenotypic variations are required to clarify the drivers and sequelae of this new MusGHV-1 variant.

Keywords: coevolution; genetic epidemiology; one health; red queen hypothesis; sexually transmitted infection.

Figure 1

DNA polymerase gene alignment containing three MusGHV-1 variants and seven other gammaherpesviruses belonging to the genus Percavirus. Red rectangles show amino acid substitutions between the three MusGHV-1 variants (numbers 1 to 3 on the list).

Figure 2

Maximum likelihood phylogenetic tree based on a portion of the polymerase gene of 10 gammaherpesvirus sequences. The alignment of sequences trimmed at 693 nucleotides was produced using MAFFT v7.450 using the G-INS-i algorithm. The tree is mid-point rooted. Bootstrap values (100 replicates) in excess of 30% are indicated at each node. The scale bar corresponds to nucleotide substitutions per site. The MusGHV-1 variants discussed in this paper (i.e., common and novel variants) are coloured in red.

Figure 3

Map of genital tract MusGHV-1 occurrence and MusGHV-1 variants distribution in badger social groups in Wytham Woods in 2018. The name of each social group is highlighted in yellow. The areas with grey colour indicate sample sizes of less than 3.

Figure 4

Ct values representing relative blood MusGHV-1 viral load of 39 blood samples collected from 23 individuals in different seasons (see Table S2 for details). The relative viral load was higher in juveniles (less than 2 years old) than in any other age class (linear mixed-effect model, t-test, p < 0.001, Table 4).