Conflict of interest statement
This work has been funded by the following grant: BFU2009-11118 from the Ministerio de Ciencia e Innovación (Spain) and 2011 CTP 00032 from the Generalitat de Catalunya (Spain). Noemí Mañé (AP2012-0897) is supported by the Ministerio de Ciencia e Innovación (Spain) and Francisco Fernández (2014FI_B00415) by the Generalitat de Catalunya (Spain). Diana Gallego is supported by the Instituto de Salud Carlos III, Centro de Investigación Biomédica en red de enfermedades hepáticas y digestivas (CIBERehd).
Bovine herpesvirus type 1 (BoHV-1) is an alpha-herpesvirus responsible for respiratory disease, abortions and genital disorders in cattle (Tikoo et al., 1995). BoHV-5, a closely related alpha-herpesvirus, is the causative agent of meningoencephalitis in calves (Pérez et al., 2002), which is highly prevalent in South America. Unlike BoHV-5, BoHV-1 has been reported only occasionally as responsible for bovine encephalitis (Meyer et al., 2001). However, several cases of neurological disease in cattle have recently been attributed to BoHV-1 (Silva et al., 2007; Rissi et al., 2008).
Neurotropic alpha-herpesviruses reach the SW033291 via the trigeminal and olfactory pathways. However, it is apparent that BoHV-1 only reaches neural tissues via the trigeminal route (Muylkens et al., 2007). Within the trigeminal ganglion (TG), BoHV-1 probably does not replicate further than first order neurons, where latency is established (d\’Offay et al., 1993). Consequently, neurological disease would not be expected to be commonly associated with BoHV-1 infection. Nevertheless, recent reports on the involvement of BoHV-1 in cases of encephalitis in cattle suggest that the virus might be able to replicate in the central nervous system (CNS).
Materials and methods
Although neurological disease associated with BoHV-1 has occasionally been documented (Silva et al., 2007; Rissi et al., 2008), it is considered that BoHV-5 is responsible for typical herpesvirus encephalitis in cattle (Pérez et al. 2002). It is widely accepted that BoHV-1 strains can only replicate focally within the CNS without further spread (Belknap et al., 1994). However, Silva et al. (2007) and Rissi et al. (2008) isolated BoHV-1 from several cases of encephalitis in cattle from southern Brazil. Similar to the findings of the present study, in both reports of natural infections, macroscopic brain lesions were not observed and microscopic lesions were detected in only a few cases.
Virological and histological data from this study demonstrated that both strains of BoHV-1 tested were able to reach and replicate within the nervous system of calves and induce lesions compatible with encephalitis. Silva et al. (2007) suggested that some BoHV-1 isolates might show an increased ability to replicate in neural tissues and cause neurological disease. Moreover, sporadic cases of encephalitis associated with BoHV-1 have been attributed to individual host susceptibility (Muylkens et al., 2007). It is likely that both factors are involved in the development of neurological disease. In our study, we show that respiratory BoHV-1 strains have neuroinvasive potential. Dix et al. (1983) postulated that viral spread is an important property of the virus to induce acute neurological disease.
Slight differences in the sites of replication in neural tissue and virulence of BoHV-1 strains were evident in this study. The amount of infectious virus in the brain does not reflect the progress of disease directly and the neuroinvasive properties of encephalitic strains are not a function of the rate of replication (Bergström and Lycke, 1990). BoHV-1.LA replicated at lower levels in the brain when compared with BoHV-1.Cooper. However, it induced evident microscopic lesions compatible with encephalitis. Similarly, BoHV-5 grows poorly in cell culture, especially when attempting isolation from brain samples (Schudel et al., 1986; Pérez et al., 2002). Nonetheless, it is the causal agent of severe cases of necrotising meningo-encephalitis in calves.
Conflict of interest statement