Susceptibility of mice to bovine herpesvirus type 5 infection in the central nervous system

Abstract

Bovine herpesvirus type 5 (BoHV-5) is an important pathogen that causes meningoencephalitis in cattle. Few studies have used the mouse as a model for BoHV-5 infection. Despite the fact that BoHV-5 can infect mice with immune deficiencies, little is known about viral replication, immune response, and the course of infection in the central nervous system (CNS) of wild-type mice. Therefore, the aim of this study was to evaluate the response in the CNS of BALB/c mice acutely infected with BoHV-5 at different days post-inoculation (dpi). BoHV-5, when inoculated intracranially, was able to infect and replicate within the CNS of BALB/c mice. Until 15 dpi, the mice were able to survive without showing prominent neurological signs. The infection was accompanied by a Th1 immune response, with a significant expression of the cytokines IFN-γ and TNF-α and chemokine CCL-2. The expression of these cytokines and chemokines was most significant in the early course of infection (3 and 4 dpi), and it was followed by meningoencephalitis with perivascular cuffing and periventriculitis, composed mainly of macrophages and lymphocytes. After the expression of cytokines and chemokine, the mice were able to curb BoHV-5 acute infection in the brain, since there was a decrease in the number of BoHV-5 DNA copies after 3 dpi and viable viral particles were not detected after 6 dpi. Importantly, BoHV-5 was able to infect the trigeminal ganglia during acute infection, since a large number of BoHV-5 DNA copies were detected on 1 and 2 dpi.

Experimental infection of BALB/c mice with felid alphaherpesvirus 1

“…The intranasal inoculation of FHV-1 is a proven effective method to reproduce infection in mice since lesions and viral DNA can be found in the lungs as well as adjacent organs as demonstrated in cats (G. F. McGregor, Sheehan, & Simko, 2016) and in mice infected with EHV-1 (Mori et al, 2012). Such systemic infection in mice could also be detected for BoHV-5 (Mesquita et al, 2017), but the inoculation was performed intraperitoneally and with higher viral titers. Systemic disease is more likely to be caused by intraperitoneal or intravenous injections and, in contrast, peripheral infections have been initiated by ocular, vaginal, skin, and nasal/oral tissue inoculations (Kollias, Huneke, Wigdahl, & Jennings, 2015).…”

“…There are several reports on the reproduction of herpesvirus infections in animal models, such as bovine herpesvirus 5 (BoHV-5), equid herpesvirus type 1 (EHV-1), and herpes simplex types 1 and 2 (HSV-1 and HSV-2) (Mesquita et al, 2017;Mahiet et al, 2012;Mori et al, 2012). However, to date, no studies have examined the reproduction of FHV-1 infections in animal models except in the cat itself (Rodriguez, Köhler, & Kipar, 2018).…”