The Herpesvirus Nuclear Egress Complex Component, UL31, Can Be Recruited to Sites of DNA Damage Through Poly-ADP Ribose Binding

Sherry, Maxwell R; Hay, Thomas J. M.; Gulak, Michael A.; Nassiri, Arash; Finnen, Renée L.; Banfield, Bruce W.

doi:10.1038/s41598-017-02109-0

Cited by 12 publications

(18 citation statements)

References 61 publications

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“…Plasmids and transfections. The construction of a plasmid encoding EGFP-UL31 was described previously (36). To construct EGFP-UL34, PCR utilizing the forward primer 5=-AGTTCGAATTCTATGGCGG GGATGGGGAAGCCCTACG-3= and the reverse primer 5=-GATCGTCGACTCATATAGGCGCGCGCCAACCGC C-3= were used to amplify the UL34 gene using purified HSV-2 DNA as the template.…”

Section: Supplemental Materialsmentioning

confidence: 99%

Differentiating the Roles of UL16, UL21, and Us3 in the Nuclear Egress of Herpes Simplex Virus Capsids

Gao

Finnen

Sherry

et al. 2020

J Virol

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Viral proteins pUL16 and pUL21 are required for efficient nuclear egress of herpes simplex virus 2 capsids. To better understand the role of these proteins in nuclear egress, we established whether nuclear egress complex (NEC) distribution and/or function was altered in the absence of either pUL16 or pUL21. NEC distribution in cells infected with pUL16-deficient viruses was indistinguishable from that observed in cells infected with wild-type viruses. In contrast, NEC distribution was aberrant in cells infected with pUL21-deficient virus and, instead, showed some similarity to the aberrant NEC distribution pattern observed in cells infected with pUs3-deficient virus. These results indicated that pUL16 plays a role in nuclear egress that is distinct from that of pUL21 and pUs3. Higher-resolution examination of nuclear envelope ultrastructure in cells infected with pUL21-deficient viruses by transmission electron microscopy showed different types of nuclear envelope perturbations, including some that were not observed in cells infected with pUs3 deficient virus. The formation of the nuclear envelope perturbations observed in pUL21-deficient virus infections was dependent on a functional NEC, revealing a novel role for pUL21 in regulating NEC activity. The results of comparisons of nuclear envelope ultrastructure in cells infected with viruses lacking pUs3, pUL16, or both pUs3 and pUL16 were consistent with a role for pUL16 in advance of primary capsid envelopment and shed new light on how pUs3 functions in nuclear egress. IMPORTANCE The membrane deformation activity of the herpesvirus nuclear egress complex (NEC) allows capsids to transit through both nuclear membranes into the cytoplasm. NEC activity must be precisely controlled during viral infection, and yet our knowledge of how NEC activity is controlled is incomplete. To determine how pUL16 and pUL21, two viral proteins required for nuclear egress of herpes simplex virus 2, function in nuclear egress, we examined how the lack of each protein impacted NEC distribution. These analyses revealed a function of pUL16 in nuclear egress distinct from that of pUL21, uncovered a novel role for pUL21 in regulating NEC activity, and shed new light on how a viral kinase, pUs3, regulates nuclear egress. Nuclear egress of capsids is required for all herpesviruses. A complete understanding of all aspects of nuclear egress, including how viral NEC activity is controlled, may yield strategies to disrupt this process and aid the development of herpes-specific antiviral therapies.

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Section: Supplemental Materialsmentioning

confidence: 99%

Differentiating the Roles of UL16, UL21, and Us3 in the Nuclear Egress of Herpes Simplex Virus Capsids

Gao

Finnen

Sherry

et al. 2020

J Virol

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“…DDR factors may also play roles at late stages of infection. For example, DDR signaling could be coupled to nuclear egress by recruiting the egress complex component UL31 through poly-ADP ribose binding (77).…”

Section: Viral Activation and Modulation Of Dna Damage Response Signamentioning

confidence: 99%

Virus DNA Replication and the Host DNA Damage Response

2018

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Viral DNA genomes have limited coding capacity and therefore harness cellular factors to facilitate replication of their genomes and generate progeny virions. Studies of viruses and how they interact with cellular processes have historically provided seminal insights into basic biology and disease mechanisms. The replicative life cycles of many DNA viruses have been shown to engage components of the host DNA damage and repair machinery. Viruses have evolved numerous strategies to navigate the cellular DNA damage response. By hijacking and manipulating cellular replication and repair processes, DNA viruses can selectively harness or abrogate distinct components of the cellular machinery to complete their life cycles. Here, we highlight consequences for viral replication and host genome integrity during the dynamic interactions between virus and host.

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“…The construction of a plasmid encoding EGFP-UL31 was described previously (36). To construct EGFP-UL34, PCR utilizing a forward primer 5’-AGTTCGAATTCTATGGCGGGGATGGGGAAGCCCTACG-3’ and reverse primer 5’-GATCGTCGACTCATATAGGCGCGCGCCAACCGCC-3’ were used to amplify the UL34 gene using purified HSV-2 DNA as template.…”

Section: Methodsmentioning

confidence: 99%

Differentiating the Roles of UL16, UL21 and Us3 in the Nuclear Egress of Herpes Simplex Virus Capsids

Gao

Finnen

Sherry

et al. 2020

Preprint

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AbstractPrevious studies from our laboratory established that pUL16 and pUL21 are required for efficient nuclear egress of herpes simplex type 2 (HSV-2) capsids. To better understand the role of these proteins in nuclear egress, we wished to establish whether nuclear egress complex (NEC) localization and/or function was altered in the absence of either pUL16 or pUL21. We used antiserum raised against HSV-2 NEC components pUL31 and pUL34 to examine NEC localization by immunofluorescence microscopy. NEC localization in cells infected with pUL16 deficient viruses was indistinguishable from that observed in cells infected with wild type viruses. By contrast, NEC localization was found to be aberrant in cells infected with pUL21 deficient virus and, instead, showed some similarity to the aberrant NEC localization pattern observed in cells infected with pUs3 deficient virus. These results indicated that pUL16 plays a role in nuclear egress that is distinct from that of pUL21 and pUs3. Higher resolution examination of nuclear envelope ultrastructure in cells infected with pUL21 deficient viruses by transmission electron microscopy showed different types of nuclear envelope perturbations, including some that were not observed in cells infected with pUs3 deficient virus. The formation of the nuclear envelope perturbations observed in pUL21 deficient virus infections was found to be dependent on a functional NEC, revealing a novel role for pUL21 in regulating NEC activity. The results of comparisons of nuclear envelope ultrastructure in cells infected with viruses lacking pUs3, pUL16 or both pUs3 and pUL16 were consistent with a role for pUL16 upstream of primary capsid envelopment and shed new light on how pUs3 functions in nuclear egress.Author summaryThe membrane deformation activity of the herpesvirus nuclear egress complex (NEC), allows viral capsids to transit from their site of assembly in the nucleus through both nuclear membranes into the cytoplasm. The timing, extent and directionality of NEC activity must be precisely controlled during viral infection, yet our knowledge of how NEC activity is controlled is incomplete. To determine how pUL16 and pUL21, two viral proteins required for nuclear egress of herpes simplex virus type 2 (HSV-2) capsids, function to promote nuclear egress, we examined how the lack of each protein impacted NEC localization. These analyses revealed a function of pUL16 in nuclear egress that is distinct from that of pUL21, uncovered a novel role for pUL21 in regulating NEC activity and shed new light on how a viral kinase, pUs3, regulates nuclear egress. Nuclear egress of viral capsids is a common feature of the replicative cycle of all herpesviruses. A complete understanding of all aspects of nuclear egress, including how viral NEC activity is controlled, may yield strategies to disrupt this process that could be applied to the development of herpes-specific antiviral drugs.

show abstract

The Herpesvirus Nuclear Egress Complex Component, UL31, Can Be Recruited to Sites of DNA Damage Through Poly-ADP Ribose Binding

Cited by 12 publications

References 61 publications

Differentiating the Roles of UL16, UL21, and Us3 in the Nuclear Egress of Herpes Simplex Virus Capsids

Differentiating the Roles of UL16, UL21, and Us3 in the Nuclear Egress of Herpes Simplex Virus Capsids

Virus DNA Replication and the Host DNA Damage Response

Differentiating the Roles of UL16, UL21 and Us3 in the Nuclear Egress of Herpes Simplex Virus Capsids

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