Ivermectin blocks the nuclear location signal of parvoviruses in crayfish, Cherax quadricarinatus

Abstract

Parvoviruses have been responsible for major problems in the shrimp aquaculture for decades with few options for control apart from avoidance. As intranuclear viruses for some of their replication, parvoviruses need to use the cell's nuclear transport signals for entry into the nucleus. This study was conducted to see if ivermectin which has recently been shown to block importins in vitro would do so against two presumptive parvoviruses in a freshwater crayfish, Cherax quadricarinatus, model. Crayfish were shown to tolerate ivermectin at 7 μg/kg injected intramuscularly and survival appeared to be enhanced with increasing dose (P ≤ 0.1). Ivermectin dramatically decreased hypertrophied nuclei caused by presumptive gill parvovirus by ~ 68% (P ≤ 0.001) after 2 doses of 7 μg/kg reducing from 1591 to 505 affected cells in the gills. The reduction did not increase further with increasing doses. Also, ivermectin appeared to increase the survival of crayfish when challenged with C. quadricarinatus parvo-like virus (CqPV) to levels statistically equivalent to non-infected crayfish but did not appear to affect the number of viral infected cells. There was a negative correlation between the size of crayfish and their longevity (P ≤ 0.05, R2 = 0.15) with smaller crayfish dying faster when challenged with CqPV. This is the first in vivo testing of ivermectin against viruses and showed that ivermectins do dramatically block some parvoviruses, possibly by interactions with cellular importins. There may be a therapeutic role for ivermectins in viral reduction in broodstock in crustacean aquaculture.