Heliothis zea Nudivirus 1 Gene hhi1 Induces Apoptosis Which Is Blocked by the Hz-iap2 Gene and a Noncoding Gene, pag1

Abstract

Heliothis zea nudivirus 1 (HzNV-1 or Hz-1 virus), previously regarded as a nonoccluded baculovirus, recently has been placed in the Nudivirus genus. This virus generates HzNV-1 HindIII-I 1 (hhi1) and many other transcripts during productive viral infection; during latent viral infection, however, persistency-associated gene 1 (pag1) is the only gene expressed. In this report, we used transient expression assays to show that hhi1 can trigger strong apoptosis in transfected cells, which can be blocked, at least partially, by the inhibitor of apoptosis genes Autographa californica iap2 (Ac-iap2) and H. zea iap2 (Hz-iap2). In addition to these two genes, unexpectedly, pag1, which encodes a noncoding RNA with no detectable protein product, was found to efficiently suppress hhi1-induced apoptosis. The assay of pro-Sf-caspase-1 processing by hhi1 transfection did not detect the small P12 subunit at any of the time intervals tested, suggesting that hhi1 of HzNV-1 induces apoptosis through alternative caspase pathways.

Viral IAPs, then and now

“…Asterisks indicate predicted zinc-chelating residues, based on known BIR and RING structures. that was induced by expression of a non-coding HzNV-1 transcript called hhi1 [46]. Apoptosis induced by hhi1 expression appeared to activate only select effector caspases in SF-21 cells, as effector caspase activity was observed, but apparently without activation of SF-caspase-1, which is the major effector caspase in these cells [47].…”

“…Outside of the baculoviruses, viral IAPs have been biologically characterized from members of Asfarviridae [30], Iridoviridae [31], Entomopoxvirinae [28], Nudiviridae [46], and Ascoviridae [32]. Except for the ascovirus homolog, which has an incomplete BIR [32], these other viral IAPs were all found to have anti-apoptotic activity.…”

Baculovirus IE2 Stimulates the Expression of Heat Shock Proteins in Insect and Mammalian Cells to Facilitate Its Proper Functioning

“…Construction of pKShE was as described previously [ 30 ]. To generate IE2-expressing plasmid for the insect system, pKShIE2, the AcMNPV ie2 gene was amplified from pAcIE2 using IE2-F and IE2-R primers and inserted into linearized vector, which was amplified from pKShE by primers pKShE-F and pKShE-R, excluding the egfp gene.…”

Viral lncRNA: A regulatory molecule for controlling virus life cycle

“…Additionally, some non-coding genes can act as bi-functional factors to promote viral entry or the maintenance of a latent state. The non-coding gene Pag1 blocks the HzNV-1 gene hhi to establish viral latency by encoding two miRNAs that target and degrade the hhi1 transcript, which is a stimulator of apoptosis [29] , [30] . PAT1, which is another non-coding transcript encoded by pag1, has also been verified to be involved in persistent infection in cells.…”