Atividade do ganciclovir em coelhos inoculados com o alfaherpesvírus equino 1

Abstract

Equine alfaherpervirus 1 (EHV-1), a member of the family Herpesviridae and subfamily Alphaherpesvirinae, is distributed worldwide and associated with abortions, respiratory and neurological disease in horses. No specific treatment for diseases associated with EHV-1 in horses is available, since human anti-herpetic drugs are not yet routinely used in equine medicine. Thus, the objective of this study was to investigate the in vivo anti-herpetic activity of ganciclovir (GCV), a nucleoside analogue drug used in the herpesvirus infections treatment in humans, against EHV-1. In vivo tests were performed in rabbits, an experimental model for EHV-1 respiratory disease. For this, eighteen New Zealand rabbits with approximately 30 days of age were alocated into three groups of 6 animals each and each group received a treatment: (G1) inoculated by the intranasal route (IN) with RPMI medium; (G2) inoculated by the IN route with 107 DICC50 of EHV-1 strain Kentucky D and (G3) inoculated with EHV-1 and treated with GCV (intravenously with 2.5mg / kg every 12h for 7 days). After inoculation, the animals were monitored for clinical, virological and pathological aspects for 15 days. All animals of G2 developed systemic signs (apathy, inappetence) and respiratory signs of variable severity between days 3 and 13 pi. These signs consisted of serous to mucopurulent nasal secretion and mild to severe respiratory distress, as well as ocular secretion. In addition, these animals presented lower weight gain than the control (G1) and GCV (G3) groups at days 4, 6, 10, 12 and 14 pi (p <0.05). A rabbit from this group presented neurological signs and died on day three after inoculation (pi). The presence of the virus in the lung of this animal was confirmed by viral isolation and histopathology. In contrast, animals from the G3 group (inoculated with EHV-1 and treated with GCV) showed no systemic signs and presented only mild serous nasal secretion. The weight gain of these animals was similar to those of the control group (G1) and higher than those of the G2 group at days 4, 6, 10, 12 and 14 pi (p <0.05). Viral excretion in secretions and seroconversion to EHV-1 were observed in both G2 and G3 animals, with no evident differences in magnitude and duration. Thus, GCV treatment in rabbits infected with EHV-1 (G3) resulted in maintenance of daily weight gain, abolition of systemic signs and significant attenuation of respiratory clinical signs. These results are promising for the use of GCV in the treatment of herpes infections in horses. However, further studies investigating different doses, frequency of administration and activity when administered after the onset of clinical signs are necessary prior to its use in this species.