Identification of a novel host protein SINAL10 interacting with GP64 and its role in Bombyx mori nucleopolyhedrovirus infection

Feng, Mei; Kong, Xiaodong; Zhang, Jianjia; Xu, Weifan; Wu, Xiaoxia

doi:10.1016/j.virusres.2018.02.005

Cited by 20 publications

(18 citation statements)

References 38 publications

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“…Instead, herpesviruses dissolve the nuclear lamina, a dense meshwork under their inner nuclear membrane (INM), and then nucleocapsids bud from the nucleus into the INM and form enveloped particles in the perinuclear space; these perinuclear enveloped particles then fuse with the outer nuclear membranes (ONM), become deenveloped particles, and eventually are released to the cytoplasm (4,8). Similarly, for viruses in the Baculoviridae family with circular dsDNA genomes packaged into rod-shaped, enveloped nucleocapsids (9,10), the most common way of nuclear egress observed in studies of nucleopolyhedrovirus (NPV) is dependent on the membrane budding pathway (9,11). Parvoviruses, which are nonenveloped single-stranded DNA viruses, traverse the NE via alteration of the permeability of nuclear pores or destruction of NE continuity (12).…”

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confidence: 99%

Cellular p32 Is a Critical Regulator of Porcine Circovirus Type 2 Nuclear Egress

Wang

Niu

et al. 2019

J Virol

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Circoviruses are the smallest DNA viruses known to infect mammalian and avian species. Although circoviruses are known to be associated with a range of clinical diseases, the details of circovirus DNA release still remain unknown. Here, we identified p32 as a key regulator for porcine circoviral nuclear egress. Upon porcine circovirus type 2 (PCV2) infection, p32 was recruited into the nucleus by the viral capsid (Cap) protein; simultaneously, protein kinase C isoform δ (PKC-δ) was phosphorylated at threonine 505 by phospholipase C (PLC)-mediated signaling at the early stage of infection, which was further amplified by Jun N-terminal protein kinase (JNK) and extracellular signal-regulated kinase (ERK) signaling at the late infection phase. p32 functioned as an adaptor to recruit phosphorylated PKC-δ and Cap to the nuclear membrane to phosphorylate lamin A/C, resulting in a rearrangement of nuclear lamina and thus facilitating viral nuclear egress. Consistent with these findings, knockout (KO) of p32 in PCV2-infected cells markedly reduced the phosphorylation of PKC-δ and impeded the recruitment of p-PKC-δ and Cap to the nuclear membrane, hence abolishing the phosphorylation of lamin A/C and the rearrangement of nuclear lamina. As a result, p32 depletion profoundly impaired the production of cell-free viruses during PCV2 infection. We further identified the N-terminal 24RRR26 of Cap to be crucial for binding to p32, and mutation of these three arginine residues significantly weakened the replication and pathogenesis of PCV2 in vivo. In summary, our findings highlight a critical role of p32 in the activation and recruitment of PKC-δ to phosphorylate lamin A/C and facilitate porcine circoviral nuclear egress, and they certainly help understanding of the mechanism of PCV2 replication. IMPORTANCE Circovirus infections are highly prevalent in mammalian and avian species. Circoviral capsid protein is the only structural protein of the virion that plays an essential role in viral assembly. However, the machinery of circovirus nuclear egress is currently unknown. In this work, we identified p32 as a key regulator of porcine circovirus type 2 (PCV2) nuclear egress that forms a complex with the viral capsid (Cap) protein to enhance protein kinase C isoform δ (PKC-δ) activity; this resulted in a recruitment of phosphorylated PKC-δ to the nuclear membrane, which further phosphorylates lamin A/C to promote the rearrangement of nuclear lamina and facilitate viral nuclear egress. Notably, we found that the N-terminal 24RRR26 of Cap, a highly conserved motif among circovirus species, was required for interacting with p32, and that mutation of this motif markedly impeded PCV2 nuclear egress. These data indicate that p32 is a critical regulator of PCV2 nuclear egress and reveal the importance of this finding in circovirus replication.

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confidence: 99%

Cellular p32 Is a Critical Regulator of Porcine Circovirus Type 2 Nuclear Egress

Wang

Niu

et al. 2019

J Virol

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“…As an example, injections of siRNAs into silkworm eggs caused even stronger knockdown effects than dsRNAs (Yamaguchi et al , ). Moreover, siRNAs were also used successfully to knock down a silkworm E3 ubiquitin‐protein ligase to inhibit reproduction of Bombyx mori nucleopolyhedrovirus (Feng et al , ), and to knock down a silkworm Toll ligand, spatzle3, to disrupt melanization implicated in stripe pattern formation (KonDo et al , ). In addition, siRNAs (20–25 nt) can be easily synthesized, making them more cost‐effective than dsRNAs (100–500 bp).…”

Section: Resultsmentioning

confidence: 99%

Vacuolar protein sorting 4 is required for silkworm metamorphosis

Xia

Chen

Shao

et al. 2019

Insect Molecular Biology

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Vacuolar protein sorting 4 (Vps4) not only functions with its positive regulator vacuolar protein sorting 20‐associated 1 (Vta1) in the multivesicular body (MVB) pathway but also participates alone in MVB‐unrelated cellular processes. However, its physiological roles at the organism level remain rarely explored. We previously identified their respective homologues Bombyx mori Vps4 (BmVps4) and BmVta1 from the silkworm, a model organism for insect research. In this study, we performed fluorescence quantitative real‐time PCR and Western blot to globally characterize the transcription and protein expression profiles of BmVps4 and BmVta1 during silkworm development and in different silkworm tissues and organs. The results showed that they were significantly up‐regulated in metamorphosis, adulthood and embryogenesis relative to larval stages, and displayed a roughly similar tissue‐and‐organ specificity for transcriptions in silkworm larvae. Importantly, BmVps4 was down‐regulated during the early period of the fifth instar, reaching the lowest level of transcription on Day 6, then up‐regulated from Day 7 to the wandering, spinning and pupal stages, and down‐regulated again in adulthood. Moreover, knocking down BmVps4 by RNA interference significantly inhibited silk gland growth, shortened spinning time, prolonged pupation, reduced pupal size and weight, and increased moth wing defects. Together, our data demonstrate the critical and broad requirements for BmVps4 in silkworm metamorphosis.

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“…These libraries can then be utilised in GOF screening, whereby cDNA libraries developed from susceptible cell lines are transduced into non-susceptible cell lines, and retested for susceptibility. cDNA libraries have been used for receptor identification since the 1990s [9,75,76]. In 2018, a cDNA library containing 8.4 × 10 6 primary clones derived from ARPE-19 epithelial cells was used to identify genes that promote HMCV entry [76].…”

Section: Ectopic Expression Of Complementary Dnamentioning

confidence: 99%

Advances in high-throughput methods for the identification of virus receptors

Barrass

Butcher

2019

Med Microbiol Immunol

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Viruses have evolved many mechanisms to invade host cells and establish successful infections. The interaction between viral attachment proteins and host cell receptors is the first and decisive step in establishing such infections, initiating virus entry into the host cells. Therefore, the identification of host receptors is fundamental in understanding pathogenesis and tissue tropism. Furthermore, receptor identification can inform the development of antivirals, vaccines, and diagnostic technologies, which have a substantial impact on human health. Nevertheless, due to the complex nature of virus entry, the redundancy in receptor usage, and the limitations in current identification methods, many host receptors remain elusive. Recent advances in targeted gene perturbation, high-throughput screening, and mass spectrometry have facilitated the discovery of virus receptors in recent years. In this review, we compare the current methods used within the field to identify virus receptors, focussing on genomic-and interactome-based approaches.

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Identification of a novel host protein SINAL10 interacting with GP64 and its role in Bombyx mori nucleopolyhedrovirus infection

Cited by 20 publications

References 38 publications

Cellular p32 Is a Critical Regulator of Porcine Circovirus Type 2 Nuclear Egress

Cellular p32 Is a Critical Regulator of Porcine Circovirus Type 2 Nuclear Egress

Vacuolar protein sorting 4 is required for silkworm metamorphosis

Advances in high-throughput methods for the identification of virus receptors

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