Sloths host Anhanga virus‐related phleboviruses across large distances in time and space

Abstract

Sloths are genetically and physiologically divergent mammals. Phleboviruses are major arthropod‐borne viruses (arboviruses) causing disease in humans and other animals globally. Sloths host arboviruses, but virus detections are scarce. A phlebovirus termed Anhanga virus (ANHV) was isolated from a Brazilian Linnaeus's two‐toed sloth (Choloepus didactylus) in 1962. Here, we investigated the presence of phleboviruses in sera sampled in 2014 from 74 Hoffmann's two‐toed (Choloepus hoffmanni, n = 65) and three‐toed (Bradypus variegatus, n = 9) sloths in Costa Rica by broadly reactive RT‐PCR. A clinically healthy adult Hoffmann's two‐toed sloth was infected with a phlebovirus. Viral load in this animal was high at 8.5 × 107 RNA copies/ml. The full coding sequence of the virus was determined by deep sequencing. Phylogenetic analyses and sequence distance comparisons revealed that the new sloth virus, likely representing a new phlebovirus species, provisionally named Penshurt virus (PEHV), was most closely related to ANHV, with amino acid identities of 93.1%, 84.6%, 94.7% and 89.0% in the translated L, M, N and NSs genes, respectively. Significantly more non‐synonymous mutations relative to ANHV occurred in the M gene encoding the viral glycoproteins and in the NSs gene encoding a putative interferon antagonist compared to L and N genes. This was compatible with viral adaptation to different sloth species and with micro‐evolutionary processes associated with immune evasion during the genealogy of sloth‐associated phleboviruses. However, gene‐wide mean dN/dS ratios were low at 0.02–0.15 and no sites showed significant evidence for positive selection, pointing to comparable selection pressures within sloth‐associated viruses and genetically related phleboviruses infecting hosts other than sloths. The detection of a new phlebovirus closely‐related to ANHV, in sloths from Costa Rica fifty years after and more than 3,000 km away from the isolation of ANHV confirmed the host associations of ANHV‐related phleboviruses with the two extant species of two‐toed sloths.

Cross-order host switches of hepatitis C-related viruses illustrated by a novel hepacivirus from sloths

“…2018 ). It cannot be excluded that these animals may be differentially affected by systemic viral infections such as those potentially caused by HVs, compared to other mammals ( de Oliveira Filho et al. 2020 ).…”

On the move: sloths and their epibionts as model mobile ecosystems

“…Sloths are also carriers of a variety of arthropod‐associated viruses (‘arboviruses’; e.g. phleboviruses, flaviviruses, encephalitis viruses, and orthobunyaviruses) (Seymour, Peralta & Montgomery, 1983 ; Gilmore et al ., 2001 ; Medlin et al ., 2016 ; de Oliveira Filho et al ., 2020 ) and insect‐borne protozoans (e.g. trypanosomes, such as Leishmania ) (Shaw, 1985 ; Gilmore et al ., 2001 ; Muñoz‐García et al ., 2019 ).…”

Identification of animal hosts of Fort Sherman virus, a New World zoonotic orthobunyavirus

“…Viral reassortment was assessed using the Recombination Detection Package V4 (Martin et al, ) and GARD (Kosakovsky Pond, Posada, Gravenor, Woelk, & Frost, ) using an alignment containing concatenated orthobunyavirus segments. Selection pressure analyses were performed for each FSV gene using fixed effects likelihood (FEL) and single‐likelihood ancestor counting (SLAC) implemented in Datamonkey from the HYPHY package (Pond & Frost, ) and comparing the M1 versus M2 and M7 versus M8 models implemented in the CodeML program in the PAML package (Xu & Yang, ) as described previously (de Oliveira Filho et al, ). For selection pressure analyses, we included the FSV prototype strains (86MSP18) and the Argentinian strains found in mosquitoes in 1965 (CbaAr426) and 1982 (AG83‐1746), and in horses in 2013 (SFCrEq231, SFBzEq232 and SFAbCrEq238).…”