The effect of Isoprinosine treatment on persistent infection of Balb/c mice infected with murine gammaherpesvirus 68.

We demonstrated the positive effect of Isoprinosine treatment on persistent infection of Balb/c mice with murine gammaherpesvirus 68 (MHV-68). Increased number of leukocytes, increased percentage of neutrophils, elevated levels of virus-neutralizing (VN) antibodies, reduced number of atypical lymphocytes and reduced virus titers were detected in the examined organs after a 14-day treatment. The positive effect of Isoprinosine therapy vanished after 120-150 days. After this interval, we demonstrated lower numbers of leukocytes, lower levels of VN antibodies and an increased number of atypical lymphoid monocytes in the Isoprinosine-treated group. Immunological parameters correlated with increased titers of virus in all investigated organs. Evidence of immunostimulation was demonstrated by lower incidence of tumor formation (7.5%) in the group of MHV-infected and Isoprinosine-treated mice in comparison to group without Isoprinosine treatment (17.5%). The presented results showed that Isoprinosine therapy had a positive impact on persistent infection of mice with MHV-68, but this effect was time-limited. The improvement of the investigated parameters lasted for five months only. Our presented results confirmed that each treatment with Isoprinosine should be repeated and must be long-term in some chronic infections.

The influence of dual infection with herpes and influenza viruses on the differential blood cell count of mice.

Based on our previous results, which confirmed the role of latent gammaherpesvirus infection in alteration of immune homeostasis, we studied the influence of simultaneous infection with gammaherpes and influenza viruses on selected parameters of innate immunity, particularly on the subpopulations of peripheral blood cell leukocytes. The aim was to analyze changes of differential blood cell count of BALB/c mice persistently infected with murine gammaherpesvirus 68 (MHV-68) and subsequently co-infected with influenza A virus (IAV), in comparison to mice infected with MHV-68 or with IAV only. Our results showed that ongoing gammaherpesvirus latency in mice caused a decreased number of leukocytes after acute infection with IAV in comparison to a single acute IAV infection. However, increased proportion of neutrophils was measured in peripheral blood of IAV- infected and co-infected mice. Dual infection had no effect on the proportion of monocytes or basophilic and eosinophilic granulocytes. The number of atypical lymphocytes, usually accompanying the persistent infection with MHV-68, decreased in co-infected mice as a consequence of the acute infection with IAV. Persistent infection with gammaherpesvirus may thus modulate the host immune response to influenza A virus and the acute IAV infection can influence the immune homeostasis established by latent MHV-68 infection.

Simultaneous infection with gammaherpes and influenza viruses enhances the host immune defense.

We have studied the impact of simultaneous infection of mice with murine gammaherpesvirus (MHV) and influenza A virus (IAV) on the immune response and pathogenesis of both infections. After a persistent MHV-68 herpesviral infection had been established, the same mice were super-infected with IAV. Individual parameters of MHV infection (viral DNA detection in organs and blood) and numbers of leukocytes in lungs and spleens were determined. With regard to the assumed reactivation of MHV-68 (mainly in lungs, spleen, thymus and peritoneal exudate cells) we focused our attention on the detection of transcripts, typical either for lytic infection (ORF50) and/or for latency (ORF73). Herpesviral DNA was detected in above mentioned organs in several intervals during the acute phase of IAV co-infection, but the expression of monitored transcripts was lower, i.e. it has decreased. Though the reason for such limited expression during acute influenza superinfection remains unclear, it is unambiguous that lower MHV-68 expression was detected in lungs and peritoneal exudate cells (PECs) from 3rd to 10th day after co-infection with IAV. Furthermore, our study showed that the ongoing gammaherpesvirus latency in co-infected mice affected the number of cytotoxic T-lymphocytes and neutrophils during the acute IAV infection and lowered their deviations from that of non-infected mice. Therefore, we suppose that co-infection with herpes and influenza viruses could be mutually beneficial for the host by promoting its defense against both viruses.

Possible role of different animal species in maintenance and spread of murine gammaherpesvirus 68 in the nature.

Murine gammaherpesvirus 68 (MHV-68), isolated from a bank vole (Clethrionomys glareolus) in Slovakia in 1976 is a natural pathogen of wild murid rodents. This review is focused to biological properties of this pathogen, the mode of its maintenance in murid rodents as reservoir animals, mechanisms of its spread to other animals in the same biotope as well as to livestock and household animals. Potential role of ticks as vectors and the possibility of infection of humans with this virus are considered as well. All the above evidence of the virus infection of various hosts is based on serological or molecular analytical data. The presented knowledge indicates important epizootologic consequences, namely harboring and permanent maintenance of the virus in murid rodents as reservoir animals with a real possibility of spread to other animals in the same biotope. These relationships imply a cross-species virus transmission with potential serious consequences for the infected animals or humans.