Identification and functional characterization of AMVp33, a novel homolog of the baculovirus caspase inhibitor p35 found in Amsacta moorei entomopoxvirus

Means, John C.; Penabaz, Taryn; Clem, Rollie J.

doi:10.1016/j.virol.2006.08.043

Cited by 26 publications

(26 citation statements)

References 24 publications

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“…Recently, a homolog of the p35 protein, called p33, was discovered in Amsacta moorei entomopoxvirus (AmEPV), and it is the first homolog found outside of the baculoviruses (78). p33 is only 25% identical to p35 at the amino acid level but has strikingly similar predicted secondary structure and can inhibit similar effector caspases in vitro (78).…”

Section: Dronc: Drosophila Nedd2-like Caspase P35 Inhibition Of Caspamentioning

confidence: 99%

Viral Subversion of Apoptotic Enzymes: Escape from Death Row

Best

2008

Annu. Rev. Microbiol.

148

119

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To prolong cell viability and facilitate replication, viruses have evolved multiple mechanisms to inhibit the host apoptotic response. Cellular proteases such as caspases and serine proteases are instrumental in promoting apoptosis. Thus, these enzymes are logical targets for virus-mediated modulation to suppress cell death. Four major classes of viral inhibitors antagonize caspase function: serpins, p35 family members, inhibitor of apoptosis proteins, and viral FLICE-inhibitory proteins. Viruses also subvert activity of the serine proteases, granzyme B and HtrA2/Omi, to avoid cell death. The combined efforts of viruses to suppress apoptosis suggest that this response should be avoided at all costs. However, some viruses utilize caspases during replication to aid virus protein maturation, progeny release, or both. Hence, a multifaceted relationship exists between viruses and the apoptotic response they induce. Examination of these interactions contributes to our understanding of both virus pathogenesis and the regulation of apoptotic enzymes in normal cellular functions.

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Section: Dronc: Drosophila Nedd2-like Caspase P35 Inhibition Of Caspamentioning

confidence: 99%

Viral Subversion of Apoptotic Enzymes: Escape from Death Row

Best

2008

Annu. Rev. Microbiol.

148

119

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“…Thus, P49 and P35 appear to use comparable inhibitory mechanisms that depend on chemical interactions with Cys2 that anchor the inhibitor's N terminus in the caspase active site through formation of a thioester bond between caspase and inhibitor (24). The conservation of Cys2 in Amsacta moorei entomopoxvirus P33, the most distantly related P35 homolog (27), suggests that this mechanism is shared among family members.…”

Section: Discussionmentioning

confidence: 98%

“…In general, a single baculovirus species encodes only one functional inhibitor, either a substrate inhibitor or an inhibitor of apoptosis protein (IAP). P35 from the baculovirus Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) is the founding member of the family of substrate inhibitors that includes baculovirus P49 and entomopoxvirus P33 (3,9,27). Sequence comparisons have also revealed P35 homologs in Spodoptera littoralis NPV (SlNPV), Spodoptera litura NPV, Leucania separata NPV, and Bombyx mori NPV (reviewed in reference 5).…”

mentioning

confidence: 99%

Reactive-Site Cleavage Residues Confer Target Specificity to Baculovirus P49, a Dimeric Member of the P35 Family of Caspase Inhibitors

Guy

Friesen

2008

J Virol

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Baculovirus proteins P49 and P35 are potent suppressors of apoptosis in diverse organisms. Although related, P49 and P35 inhibit initiator and effector caspases, respectively, during infection of permissive insect cells. The molecular basis of this novel caspase specificity is unknown. To advance strategies for selective inhibition of the cell death caspases, we investigated biochemical differences between these baculovirus substrate inhibitors. We report here that P49 and P35 use similar mechanisms for stoichiometric inhibition that require caspase cleavage of their reactive site loops (RSL) and chemical contributions of a conserved N-terminal cysteine to stabilize the resulting inhibitory complex. Our data indicated that P49 functions as a homodimer that simultaneously binds two caspases. In contrast, P35 is a monomeric, monovalent inhibitor. P49 and P35 also differ in their RSL caspase recognition sequences. We tested the role of the P 4 -P 1 recognition motif for caspase specificity by monitoring virus-induced proteolytic processing of Sf-caspase-1, the principal effector caspase of the host insect Spodoptera frugiperda. When P49's TVTD recognition motif was replaced with P35's DQMD motif, P49 was impaired for inhibition of the initiator caspase that cleaves and activates pro-Sf-caspase-1 and instead formed a stable inhibitory complex with active Sf-caspase-1. In contrast, the effector caspase specificity of P35 was unaltered when P35's DQMD motif was replaced with TVTD. We concluded that the TVTD recognition motif is required but not sufficient for initiator caspase inhibition by P49. Our findings demonstrate a critical role for the P 4 -P 1 recognition site in caspase specificity by P49 and P35 and indicate that additional determinants are involved in target selection.The baculoviruses are large double-stranded DNA viruses of insects that trigger widespread apoptosis. To block host cell apoptosis and thereby enhance multiplication, these viruses encode diverse suppressors of apoptosis (reviewed in references 5, 6, and 14). P49 and P35 are two baculovirus-encoded apoptotic suppressors that function by inhibiting a broad range of the cell death proteases known as caspases (2,3,19,30,40,45). Although related to one another, P49 and P35 display different caspase specificities in the infected insect cell (21,22,45). Because selective inhibition of caspases may be advantageous in therapeutics for apoptosis-associated diseases, the molecular basis of target specificity by P49 and P35 is of considerable interest.The caspases are a family of cysteinyl aspartate-specific proteases that are critical effectors of apoptosis in metazoans (reviewed in references 15, 23, 32, and 33). Caspase-mediated proteolysis promotes cellular disassembly that includes chromatin condensation, nuclear DNA cleavage, membrane blebbing, and cell fragmentation. Thus, these death proteases are subject to regulation by diverse cellular and viral mechanisms (4,6,15,33,34,36). Upon apoptotic signaling, initiator caspases are autoactivated throu...

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“…A homologue for p35 (Clem & Miller, 1994) is present in MaviNPV as ORF103. So far, the p35 gene has also been found in AcMNPV, BmNPV and RoMNPV, three closely related group I NPVs, and it has homologues in Spodoptera litura nucleopolyhedrovirus (SpltNPV) (group II NPV) and in Choristoneura occidentalis granulovirus (ChocGV), as well as in Amsacta moorei entomopoxvirus (Clem et al, 1991;Du et al, 1999;Escasa et al, 2006;Kamita et al, 1993;Means et al, 2006). In contrast, iaps have been found in all members of the family Baculoviridae sequenced to date.…”

Section: Sequence Analysis Of Mavinpv Genomementioning

confidence: 99%

Genomic and host range studies of Maruca vitrata nucleopolyhedrovirus

Chen

Lee

et al. 2008

Journal of General Virology

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The complete genome of the Maruca vitrata nucleopolyhedrovirus (MaviNPV) isolated from the legume pod borer, Maruca vitrata (Lepidoptera: Pyralidae), was sequenced. It was found to be 111 953 bp in length, with an overall 39 % G+C content, and contained 126 open reading frames (ORFs) encoding predicted proteins of over 50 aa. The gene content and gene order of MaviNPV have the highest similarity to those of Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and their shared homologous genes are 100 % collinear. In fact, MaviNPV seems to be a mini-AcMNPV that is native to Taiwan and possesses a smaller genome with fewer auxiliary genes than the AcMNPV type species. Except for one ORF (Mv74), all of the MaviNPV ORFs have homologues in the AcMNPV genome. MaviNPV is the first lepidopteranspecific baculovirus to lack homologues of vfgf and odv-e66. In addition, MaviNPV lacks the baculovirus repeat ORF (bro) gene that corresponds to AcMNPV ORF2. Five homologous regions (hrs) were located within the MaviNPV genome, and these contained a total of 44 imperfect palindromes. Phylogenetic analysis of the whole genome revealed that MaviNPV was separated from the common ancestor of AcMNPV and Bombyx mori nucleopolyhedrovirus before these two viral species diverged from each other. Moreover, replication of MaviNPV in several cell lines and an egfp-MaviNPV infection assay revealed that IPLB-LD-652Y cells are only partially permissive to MaviNPV, which supports our conclusion that MaviNPV is a distinct species of the group I lepidopteran NPVs.

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Identification and functional characterization of AMVp33, a novel homolog of the baculovirus caspase inhibitor p35 found in Amsacta moorei entomopoxvirus

Cited by 26 publications

References 24 publications

Viral Subversion of Apoptotic Enzymes: Escape from Death Row

Viral Subversion of Apoptotic Enzymes: Escape from Death Row

Reactive-Site Cleavage Residues Confer Target Specificity to Baculovirus P49, a Dimeric Member of the P35 Family of Caspase Inhibitors

Genomic and host range studies of Maruca vitrata nucleopolyhedrovirus

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