Canine distemper virus in the Serengeti ecosystem: molecular adaptation to different carnivore species

Abstract

Was the 1993/1994 fatal canine distemper virus (CDV) epidemic in lions and spotted hyaenas in the Serengeti ecosystem caused by the recent spillover of a virulent domestic dog strain or one well adapted to these noncanids? We examine this question using sequence data from 13 'Serengeti' strains including five complete genomes obtained between 1993 and 2011. Phylogenetic and haplotype network analyses reveal that strains from noncanids during the epidemic were more closely related to each other than to those from domestic or wild canids. All noncanid 'Serengeti' strains during the epidemic encoded: (1) one novel substitution G134S in the CDV-V protein; and (2) the rare amino acid combination 519I/549H at two sites under positive selection in the region of the CDV-H protein that binds to SLAM (CD 150) host cell receptors. Worldwide, only a few noncanid strains in the America II lineage encode CDV-H 519I/549H. All canid 'Serengeti' strains during the epidemic coded CDV-V 134G, and CDV-H 519R/549Y, or 519R/549H. A functional assay of cell entry revealed the highest performance by CDV-H proteins encoding 519I/549H in cells expressing lion SLAM receptors, and the highest performance by proteins encoding 519R/549Y, typical of dog strains worldwide, in cells expressing dog SLAM receptors. Our findings are consistent with an epidemic in lions and hyaenas caused by CDV variants better adapted to noncanids than canids, but not with the recent spillover of a dog strain. Our study reveals a greater complexity of CDV molecular epidemiology in multihost environments than previously thought.

Social status mediates the fitness costs of infection with canine distemper virus in Serengeti spotted hyenas

“…Direct virus‐mediated damage and pro‐inflammatory cytokine‐induced damage to the central nervous system can also occur (Beineke et al., ). The CDV strain that infected hyenas in the 1993/1994 epidemic encoded one novel amino acid in the V‐protein (Nikolin et al., ). The V‐protein is known to disrupt host interferon signalling (von Messling, Svitek, & Cattaneo, ; Röthlisberger et al., ), hence rendering the outcome of infection particularly severe.…”

“…Although adults exposed to CDV before the 1993/1994 epidemic presumably had protective antibody titres, the lack of clinical canine distemper in adult hyenas during this epidemic was probably due to other components of the immune system. Hyenas, like the domestic cat Felis catus (Beineke et al., ), can have CDV replicating in leucocytes without developing clinical disease (Nikolin et al., ). Since in long‐lived species, adult survival is a critical fitness component, natural selection may also favour the development of stronger adult immune defences to minimize the impact of infections (Boots, Best, Miller, & White, ).…”

“…Multi‐event capture–mark–recapture (MECMR) models are a recent and powerful advance in statistical methods that make it possible to disentangle the effect of both processes on the infection probability and to determine the impact of infection on survival (Chambert et al., ; Conn & Cooch, ; Gimenez et al., ; Pradel, ). Here, we used this approach to assess the effect of social status in a highly social carnivore, the spotted hyena Crocuta crocuta (hereafter “hyena”) on canine distemper virus (CDV) infection during an epidemic when a strain pathogenic to this species circulated (Nikolin et al., ). CDV is a highly contagious virus of a taxonomically broad range of carnivores (Beineke, Baumgärtner, & Wohlsein, ; Deem, Spelman, Yates, & Montali, ).…”

“…clinical disease and increased mortality) were primarily observed in cubs stationed at communal dens (Haas et al., ). CDV strains that infected lions and hyenas during this epidemic were genetically distinct from those infecting canids and encoded unique mutations that most likely increased the virulence of the 1993/1994 epidemic for non‐canids (Nikolin et al., ).…”

Isolation and sequence analysis of the complete H gene of canine distemper virus from domestic dogs in Henan Province, China

“…It has been suggested that changes at amino acid positions 519, 530 and 549 of the H gene are associated with host specificity [18][19][20]. The host range of CDV strains and the outcome of infection depend on virus traits other than those affecting virus binding to SLAM receptors.…”