INTRODUCTION: Human adenovirus and herpes simplex virus cause infectious diseases of eyes, respiratory, enteric and urogenital tracts, of central and peripheral nervous system and are capable to persistence in latent form and are activated under the influence of endogenous and exogenous factors. A high spread of infections caused by herpes virus and adenovirus and their mixed infections are the problems of modern medicine. During mixed infections, an absence of viruses’ interaction as well as a mutual influence of viruses may originate. Search of drugs with a relatively high activity against the co-associated viruses by inhibiting their reproduction and transmission is an important task. Activity of antiviral drugs under condition of co-infection is not studied enough.
METHODS: Human adenovirus type 5 (HadV-5) and herpes simplex virus type 1 (HSV-1/US) were used as the model viruses. The reproduction of viruses in MDBK cells was studied using the cell-ELISA, flow cytometry and Western-blot. The levels of synthesis of the major proteins of adenoviruses and herpes viruses under conditions of the mixed infection were studied. The created model of mixed infection in the populations of MDBK cells was confirmed by the electron microscopy and immunofluorescence analysis.
The cytotoxic activity of the drugs was studied by the MTT-assay. The model of co-infection of MDBK cells was used to evaluate the efficiency of the antiviral agents of the broad action spectrum (ganciclovir, cidofovir and ribavirin) against HAdV-5 and HSV-1/US. The antiviral effects of the drugs were studied using the medical scheme of introduction of preparation (as a component of supporting medium). The analysis of the virus DNA synthesis in infected cells after treatment with the drugs was carried out by the RT-qPCR. The effectiveness of the preparations under mono- and mixed infections was studied by the cytomorphological method.
RESULTS: The simultaneous infection of the cells with two viruses resulted in a significant inhibition of the reproduction of herpes virus and in a less pronounced inhibition of the adenovirus reproduction.
Use of ribavirin in conditions of mono infection led to the inhibition of DNA replication of adenovirus by 41% and herpes virus by 29%. Ribavirin was ineffective against HАdV-5 and its activity against herpes virus remained unchanged under conditions of co-infection. The analysis of antiviral activity of ganciclovir on the models of mono infections showed the reduction of reproduction of HSV-1/US by 60% and HAdV-5 by 4%. Ganciclovir inhibited the reproduction of herpes virus by 61% during the co-infection. The effectiveness of the drug against adenovirus increased 20%. Under condition of the mixed infection the cidofovir activity against HAdV-5 and HSV-1/US decreased 3-fold and 79-fold, respectively, compared to the mono infections.
CONCLUSIONS: The changes of the nature of the pathological processes were found, as a result of the interference of the viruses and the differences of the drugs activities against the co-associated viruses in conditions of the mono and mixed infections of MDBK cells. Both the increase and inhibition of the drugs activities were detected that may lead to the formation of resistant strains of viruses.