Hsp70 Isoforms Are Essential for the Formation of Kaposi’s Sarcoma-Associated Herpesvirus Replication and Transcription Compartments


Molecular chaperones from the HSP70 and HSP90 families have important roles in cell survival. Recent evidence has also implicated their functioning in a variety of diseases, including cancer. As such they have been identified as emerging drug targets. Kaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenic herpesvirus which, like other herpesviruses, lytically replicates in virus-induced structures within the nucleus, termed replication and transcription compartments (RTCs). Here we developed a novel proteomic approach enhanced by subcellular fractionation to study the cellular protein composition of KSHV-induced RTCs. Results revealed that the constitutively expressed Hsc70 and the stress-inducible iHsp70 chaperones were significantly increased in the KSHV-induced RTCs. Importantly, inhibition of the ATPase function of these chaperones led to a marked reduction in KSHV RTCs formation and KSHV lytic replication. Notably, these results highlight the therapeutic potential of HSP70 inhibitors for the treatment of KSHV-related diseases, such as Kaposi’s sarcoma.


Vyšlo v časopise: Hsp70 Isoforms Are Essential for the Formation of Kaposi’s Sarcoma-Associated Herpesvirus Replication and Transcription Compartments. PLoS Pathog 11(11): e32767. doi:10.1371/journal.ppat.1005274
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.ppat.1005274

Souhrn

Molecular chaperones from the HSP70 and HSP90 families have important roles in cell survival. Recent evidence has also implicated their functioning in a variety of diseases, including cancer. As such they have been identified as emerging drug targets. Kaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenic herpesvirus which, like other herpesviruses, lytically replicates in virus-induced structures within the nucleus, termed replication and transcription compartments (RTCs). Here we developed a novel proteomic approach enhanced by subcellular fractionation to study the cellular protein composition of KSHV-induced RTCs. Results revealed that the constitutively expressed Hsc70 and the stress-inducible iHsp70 chaperones were significantly increased in the KSHV-induced RTCs. Importantly, inhibition of the ATPase function of these chaperones led to a marked reduction in KSHV RTCs formation and KSHV lytic replication. Notably, these results highlight the therapeutic potential of HSP70 inhibitors for the treatment of KSHV-related diseases, such as Kaposi’s sarcoma.


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