Evaluation of Histone Demethylase Inhibitor ML324 and Acyclovir against Cyprinid herpesvirus 3 Infection.

Cyprinid herpesvirus 3 (CyHV-3) can cause severe disease in koi and common carp (Cyprinus carpio). Currently, no effective treatment is available against CyHV-3 infection in koi. Both LSD1 and JMJD2 are histone demethylases (HD) and are critical for immediate-early (IE) gene activation essential for lytic herpesvirus replication. OG-L002 and ML324 are newly discovered specific inhibitors of LSD1 and JMJD2, respectively. Here, HD inhibitors were compared with acyclovir (ACV) against CyHV-3 infection in vitro and in vivo. ML324, at 20-50 µM, can completely block ~1 × 103 PFU CyHV-3 replication in vitro, while OG-L002 at 20 µM and 50 µM can produce 96% and 98% inhibition, respectively. Only about 94% inhibition of ~1 × 103 PFU CyHV-3 replication was observed in cells treated with ACV at 50 µM. As expected, CyHV-3 IE gene transcription of ORF139 and ORF155 was blocked within 72 h post-infection (hpi) in the presence of 20 µM ML324. No detectable cytotoxicity was observed in KF-1 or CCB cells treated for 24 h with 1 to 50 µM ML324. A significant reduction of CyHV-3 replication was observed in ~6-month-old infected koi treated with 20 µM ML324 in an immersion bath for 3-4 h at 1-, 3-, and 5-days post-infection compared to the control and ACV treatments. Under heat stress, 50-70% of 3-4-month-old koi survived CyHV-3 infection when they were treated daily with 20 µM ML324 in an immersion bath for 3-4 h within the first 5 d post-infection (dpi), compared to 11-19% and 22-27% of koi in the control and ACV treatments, respectively. Our study demonstrates that ML324 has the potential to be used against CyHV-3 infection in koi.

Attachment bonds between domestic cats and humans.

Worldwide, domestic cats (Felis silvestris catus) outnumber domestic dogs (Canis familiaris). Despite cats' success in human environments, dog social cognition has received considerably more scientific attention over the last several decades [1-3]. A key aspect of what has been said to make dogs unique is their proclivity for forming attachment bonds, including secure attachments to humans [1,3], which could provide scaffolding for the development of human-like socio-cognitive abilities and contribute to success in human environments [3]. Cats, like dogs, can be found living in social groups or solitarily, depending on early developmental factors, resource distribution, and lifetime experiences such as human interaction [1,2,4]. Despite fewer studies, research suggests we may be underestimating cats' socio-cognitive abilities [2]. Here we report evidence, using behavioral criteria established in the human infant literature [5,6], that cats display distinct attachment styles toward human caregivers. Evidence that cats share social traits once attributed to dogs and humans alone would suggest that broader non-canine-specific mechanisms may be needed to explain cross-species attachment and socio-cognitive abilities.