Naslov
Antiviral activity of H-7 on the replication of murine cytomegalovirus

Autori
Kučić, Natalia ; Mahmutefendić, Hana ; Lučin, Pero

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Abstract book (P122), FEBS Lecture Course on Cellular Signaling & 4th Dubrovnik Signaling Conference / Đikić, Ivan ; Husnjak, Koraljka - Zagreb : Institut Ruđer Bošković, 2004, 183-184

Skup
FEBS Lecture Course on Cellular Signaling & 4th Dubrovnik Signaling Conference

Mjesto i datum
Dubrovnik, Hrvatska, 21.05.2004. - 27.05.2004

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
MCMV; PKC; PKA; H7

Sažetak
Objectives: Immediately after the murine cytomegalovirus (MCMV) infection of fibroblasts the phosphoprotein pp89 (IE1), which is the product of immediate-early phase of viral replication is expressed in the cell nucleus. The protein of the early phase of viral replication (E1) is expressed afterwards. Both viral proteins could be detected in the cell nucleus 2-3 hours post infection and be used as indicators of viral DNA entry in this compartment. The aim of the present study was to further illuminate the early events of MCMV entry into the cell nucleus leading to the initiation of a productive infection cycle. Methods of study: We have studied the early events of the MCMV replication cycle by using the protein kinase inhibitors. MCMV IE1 and E1 proteins were followed by immunofluorescence and Western blot analysis. Productivity of infection was determened in the cell culture by viral titers using standard plaque forming assey. Results: Inhibitory effects achieved with H-7  1-(5-isoquinolinesulfonyl)-2-methyl-piperazine dihidrochloride inhibitor was determined on the inhibition of the IE1 and E1 viral proteins expression in the cell nucleus. H-7, an inhibitor of both, PKC and PKA, partially inhibited the expression of IE1 protein and completely blocked the expression of E1 protein. Virus replication was inhibited with H-7 in a dose dependent and reversible manner, and block in replication occurred very early in infection. Obtained results were supported with other, more specific inhibitors of PKC and PKA. Conclusion: A model for study of MCMV entry into the cell nucleus is based on the expression of immediate-early and early viral proteins in the cell nucleus. The results suggest that activity of PKC is crucial for MCMV replication as well as the physiological state of the cell like proteins phosphorylation mediated by PKC and PKA.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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