Dataset Information

The autophagy receptor SQSTM1/p62 is a restriction factor of HCMV infection

ABSTRACT: Background: Intrinsic defence mechanisms are pivotal host strategies to restrict viruses already at early stages of their infection. Here we addressed the question how the autophagy receptor sequestome 1 (SQSTM1/p62, herein termed p62) interfered with human cytomegalovirus (HCMV) infection. (2) Methods: CRISPR/Cas9- mediated genome editing, mass spectrometry and expression of p62 phosphovariants from recombinant HCMVs were used to address the role of p62 during infection. (3) Results: Knockout of p62 led to enhanced HCMV progeny release. Mass spectrometry revealed an interaction of p62 with cellular proteins required for nucleo-cytoplasmic transport. Phosphoproteomics further revealed that p62 is hyperphosphorylated at position S272 in HCMV-infected cells. Phosphorylated p62 showed enhanced nuclear retention, concordant with enhanced interaction with viral proteins relevant for genome replication and nuclear capsid egress. This modification led to reduced HCMV progeny release, compared to a unphosphorylated version of p62. (4) Conclusions: p62 is a restriction factor for HCMV replication The activity of the receptor appears to be regulated by phosphorylation at position S272, leading to enhanced nuclear localization, viral protein degradation and impairment of progeny production.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human) Cytomegalovirus Sp.

SUBMITTER: Uxia Gestal Mato

LAB HEAD: Lina Herhaus

PROVIDER: PXD055196 | Pride | 2025-05-13

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	20200617_MHO_LH_Hek_ChrZimmer_Igg_1.raw	Raw
	20200617_MHO_LH_Hek_ChrZimmer_Igg_2.raw	Raw
	20200617_MHO_LH_Hek_ChrZimmer_Igg_3.raw	Raw
	20200617_MHO_LH_Hek_ChrZimmer_Igg_4.raw	Raw
	20200617_MHO_LH_Hek_ChrZimmer_Igg_5.raw	Raw

Items per page:

1 - 5 of 19

Publications

The Autophagy Receptor <i>SQSTM1</i>/p62 Is a Restriction Factor of HCMV Infection.

Krämer Nadine N Mato Uxía Gestal UG Krauter Steffi S Büscher Nicole N Afifi Ahmad A Herhaus Lina L Florin Luise L Plachter Bodo B Zimmermann Christine C

Viruses 20240910 9

(1) Background: Intrinsic defense mechanisms are pivotal host strategies to restrict viruses already at early stages of their infection. Here, we addressed the question of how the autophagy receptor sequestome 1 (<i>SQSTM1</i>/p62, hereafter referred to as p62) interferes with human cytomegalovirus (HCMV) infection. (2) Methods: CRISPR/Cas9-mediated genome editing, mass spectrometry and the expression of p62 phosphovariants from recombinant HCMVs were used to address the role of p62 during infec ...[more]

PMID: 39339916

Similar Datasets

Project description:Huntington's disease (HD) is a dominantly inherited genetic disease caused by mutant huntingtin (htt) protein with expanded polyglutamine tracts. A neuropathological hallmark of HD is the presence of neuronal inclusions of mutant htt. p62 is an important regulatory protein in selective autophagy, a process by which aggregated proteins are degraded, and it is associated with several neurodegenerative disorders including HD. Here we investigated the effect of p62 depletion in three HD model mice: R6/2, HD190QG and HD120QG mice. We found that loss of p62 in these models led to longer lifespans and reduced nuclear inclusions, although cytoplasmic inclusions increased with polyglutamine length. In mouse embryonic fibroblasts (MEFs) with or without p62, mutant htt with a nuclear localization signal (NLS) showed no difference in nuclear inclusion between the two MEF types. In the case of mutant htt without NLS, however, p62 depletion increased cytoplasmic inclusions. Furthermore, to examine the effect of impaired autophagy in HD model mice, we crossed R6/2 mice with Atg5 conditional knockout mice. These mice also showed decreased nuclear inclusions and increased cytoplasmic inclusions, similar to HD mice lacking p62. These data suggest that the genetic ablation of p62 in HD model mice enhances cytoplasmic inclusion formation by interrupting autophagic clearance of polyQ inclusions. This reduces polyQ nuclear influx and paradoxically ameliorates disease phenotypes by decreasing toxic nuclear inclusions. Gene expression profiles were analyzed to examine the effects of p62 depletion in mouse with or without mutant huntingtin exon 1 To examine the effect of p62 depletion on the transcriptome of Huntington's disease model mice, we crossed p62 knockout mice with HD model mice. We extracted total RNA from the striatum of these mice at 8 weeks and used for a microaaray analysis. The samples are HD transgenic mice with p62 knockout (HD_p62KO), HD mice with normal p62 (HD_p62WT), non-HD-transgenic mice with p62 knockout (NT_p62KO), and non-HD-transgenic mice with normal p62 (NT_p62WT).

Dataset Information

The autophagy receptor SQSTM1/p62 is a restriction factor of HCMV infection

Dataset's files

Publications

The Autophagy Receptor <i>SQSTM1</i>/p62 Is a Restriction Factor of HCMV Infection.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

The autophagy receptor SQSTM1/p62 is a restriction factor of HCMV infection

Dataset's files

Publications

The Autophagy Receptor &lt;i&gt;SQSTM1&lt;/i&gt;/p62 Is a Restriction Factor of HCMV Infection.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

The Autophagy Receptor <i>SQSTM1</i>/p62 Is a Restriction Factor of HCMV Infection.