Full Viral Genome Sequencing and Phylogenomic Analysis of Feline Herpesvirus Type 1 (FHV-1) in Cheetahs (Acinonyx jubatus)

Abstract

Feline herpesvirus type 1 (FHV-1) is endemic in captive cheetahs and sporadically causes devastating disease. Modified live vaccines (MLV), intended for use in domestic cats, are used in some captive cheetah populations and have been anecdotally linked to disease in certain subpopulations. Ten FHV-1 isolates from ten captive cheetahs and one isolate from an MLV used to inoculate four of the host animals were analyzed. Viral DNA was extracted for full-genome sequencing by Illumina MiSeq with viral genomes then used for phylogenomic and recombinational analyses. The FHV-1 shed by vaccinated cheetahs were almost identical to the MLV, with few variants among viral genomes. Eight cheetah FHV-1 isolates and the MLV were grouped in a clade along with FHV-1 isolates from domestic cats in the USA. The remaining two cheetah FHV-1 isolates (unknown host vaccine status) were not associated with a clade. The likely ancestral origin of these two isolates involves recombination events between Australian domestic cat and cheetah FHV-1 isolates. Collectively, these data suggest that the MLV is capable of causing clinical disease and viral shedding in some cheetahs and represents evidence of interspecies transmission of virus between domestic and wild cats.

Keywords: Varicellovirus; cheetah; feline herpesvirus; genome sequencing; herpes; modified live vaccine; phylogenomic; vaccines; veterinary.

Figure 1

Maximum likelihood tree including all currently available feline herpesvirus type 1 (FHV-1) isolates along with canine herpesvirus (CHV-1/0194) as an outgroup (orange). Eight of ten cheetah isolates (purple) fell into Clade 1, with closest relations to one of the three modified live vaccines (MLV; black). Two cheetah isolates (MM-5 and MM-6) were sisters to FHV-1 strains previously isolated from domestic cats in Australia (green). Those strains in blue are previously analyzed FHV-1 isolates from domestic cats within the USA. CH-B strain (red) was previously isolated from China and falls outside of the clade structure but is closely genetically related to Clade 1.

Figure 2

Phylogenetic tree including all currently available FHV-1 sequences with a CHV-1 outgroup. Domestic cat FHV-1 isolates from the USA are shown in blue, one isolate from China is shown in red, isolates from Australia in green, isolates from modified live vaccines (MLV) in black, and cheetah FHV-1 isolates are shown in purple. Four clades are shown: Clade 1 includes only USA isolates (with vaccine strains and cheetah strains), Clade 2 includes both Australian and USA isolates, and Clade 3 and Clade 4 contain only Australian isolates. Mean interclade distances were calculated using MEGAX. MM-2, MM-3, MM-7, and MM-9 were isolated from cheetahs known to be vaccinated with the Merial brand MLV. All 4 of these isolates show a very high degree of similarity to the MLV.