PNMA2 forms immunogenic non-enveloped virus-like capsids associated with paraneoplastic neurological syndrome

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PNMA2 forms immunogenic non-enveloped virus-like capsids associated with paraneoplastic neurological syndrome. / Xu, Junjie; Erlendsson, Simon; Singh, Manvendra; Holling, G. Aaron; Regier, Matthew; Ibiricu, Iosune; Einstein, Jenifer; Hantak, Michael P.; Day, Gregory S.; Piquet, Amanda L.; Smith, Tammy L.; Clardy, Stacey L.; Whiteley, Alexandra M.; Feschotte, Cédric; Briggs, John A.G.; Shepherd, Jason D.

In: Cell, Vol. 187, No. 4, 2024, p. 831-845.e19.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Xu, J, Erlendsson, S, Singh, M, Holling, GA, Regier, M, Ibiricu, I, Einstein, J, Hantak, MP, Day, GS, Piquet, AL, Smith, TL, Clardy, SL, Whiteley, AM, Feschotte, C, Briggs, JAG & Shepherd, JD 2024, 'PNMA2 forms immunogenic non-enveloped virus-like capsids associated with paraneoplastic neurological syndrome', Cell, vol. 187, no. 4, pp. 831-845.e19. https://doi.org/10.1016/j.cell.2024.01.009

APA

Xu, J., Erlendsson, S., Singh, M., Holling, G. A., Regier, M., Ibiricu, I., Einstein, J., Hantak, M. P., Day, G. S., Piquet, A. L., Smith, T. L., Clardy, S. L., Whiteley, A. M., Feschotte, C., Briggs, J. A. G., & Shepherd, J. D. (2024). PNMA2 forms immunogenic non-enveloped virus-like capsids associated with paraneoplastic neurological syndrome. Cell, 187(4), 831-845.e19. https://doi.org/10.1016/j.cell.2024.01.009

Vancouver

Xu J, Erlendsson S, Singh M, Holling GA, Regier M, Ibiricu I et al. PNMA2 forms immunogenic non-enveloped virus-like capsids associated with paraneoplastic neurological syndrome. Cell. 2024;187(4):831-845.e19. https://doi.org/10.1016/j.cell.2024.01.009

Author

Xu, Junjie ; Erlendsson, Simon ; Singh, Manvendra ; Holling, G. Aaron ; Regier, Matthew ; Ibiricu, Iosune ; Einstein, Jenifer ; Hantak, Michael P. ; Day, Gregory S. ; Piquet, Amanda L. ; Smith, Tammy L. ; Clardy, Stacey L. ; Whiteley, Alexandra M. ; Feschotte, Cédric ; Briggs, John A.G. ; Shepherd, Jason D. / PNMA2 forms immunogenic non-enveloped virus-like capsids associated with paraneoplastic neurological syndrome. In: Cell. 2024 ; Vol. 187, No. 4. pp. 831-845.e19.

Bibtex

@article{d4b1dece99404e118a4e4cec47985d5e,
title = "PNMA2 forms immunogenic non-enveloped virus-like capsids associated with paraneoplastic neurological syndrome",
abstract = "The paraneoplastic Ma antigen (PNMA) proteins are associated with cancer-induced paraneoplastic syndromes that present with an autoimmune response and neurological symptoms. Why PNMA proteins are associated with this severe autoimmune disease is unclear. PNMA genes are predominantly expressed in the central nervous system and are ectopically expressed in some tumors. We show that PNMA2, which has been co-opted from a Ty3 retrotransposon, encodes a protein that is released from cells as non-enveloped virus-like capsids. Recombinant PNMA2 capsids injected into mice induce autoantibodies that preferentially bind external “spike” PNMA2 capsid epitopes, whereas a capsid-assembly-defective PNMA2 protein is not immunogenic. PNMA2 autoantibodies in cerebrospinal fluid of patients with anti-Ma2 paraneoplastic disease show similar preferential binding to spike capsid epitopes. PNMA2 capsid-injected mice develop learning and memory deficits. These observations suggest that PNMA2 capsids act as an extracellular antigen, capable of generating an autoimmune response that results in neurological deficits.",
keywords = "autoimmune disorder, capsid, Gag, intercellular signaling, paraneoplastic disorder, PNMA, retrotransposon, retrovirus, virus",
author = "Junjie Xu and Simon Erlendsson and Manvendra Singh and Holling, {G. Aaron} and Matthew Regier and Iosune Ibiricu and Jenifer Einstein and Hantak, {Michael P.} and Day, {Gregory S.} and Piquet, {Amanda L.} and Smith, {Tammy L.} and Clardy, {Stacey L.} and Whiteley, {Alexandra M.} and C{\'e}dric Feschotte and Briggs, {John A.G.} and Shepherd, {Jason D.}",
note = "Publisher Copyright: {\textcopyright} 2024 Elsevier Inc.",
year = "2024",
doi = "10.1016/j.cell.2024.01.009",
language = "English",
volume = "187",
pages = "831--845.e19",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "4",

}

RIS

TY - JOUR

T1 - PNMA2 forms immunogenic non-enveloped virus-like capsids associated with paraneoplastic neurological syndrome

AU - Xu, Junjie

AU - Erlendsson, Simon

AU - Singh, Manvendra

AU - Holling, G. Aaron

AU - Regier, Matthew

AU - Ibiricu, Iosune

AU - Einstein, Jenifer

AU - Hantak, Michael P.

AU - Day, Gregory S.

AU - Piquet, Amanda L.

AU - Smith, Tammy L.

AU - Clardy, Stacey L.

AU - Whiteley, Alexandra M.

AU - Feschotte, Cédric

AU - Briggs, John A.G.

AU - Shepherd, Jason D.

N1 - Publisher Copyright: © 2024 Elsevier Inc.

PY - 2024

Y1 - 2024

N2 - The paraneoplastic Ma antigen (PNMA) proteins are associated with cancer-induced paraneoplastic syndromes that present with an autoimmune response and neurological symptoms. Why PNMA proteins are associated with this severe autoimmune disease is unclear. PNMA genes are predominantly expressed in the central nervous system and are ectopically expressed in some tumors. We show that PNMA2, which has been co-opted from a Ty3 retrotransposon, encodes a protein that is released from cells as non-enveloped virus-like capsids. Recombinant PNMA2 capsids injected into mice induce autoantibodies that preferentially bind external “spike” PNMA2 capsid epitopes, whereas a capsid-assembly-defective PNMA2 protein is not immunogenic. PNMA2 autoantibodies in cerebrospinal fluid of patients with anti-Ma2 paraneoplastic disease show similar preferential binding to spike capsid epitopes. PNMA2 capsid-injected mice develop learning and memory deficits. These observations suggest that PNMA2 capsids act as an extracellular antigen, capable of generating an autoimmune response that results in neurological deficits.

AB - The paraneoplastic Ma antigen (PNMA) proteins are associated with cancer-induced paraneoplastic syndromes that present with an autoimmune response and neurological symptoms. Why PNMA proteins are associated with this severe autoimmune disease is unclear. PNMA genes are predominantly expressed in the central nervous system and are ectopically expressed in some tumors. We show that PNMA2, which has been co-opted from a Ty3 retrotransposon, encodes a protein that is released from cells as non-enveloped virus-like capsids. Recombinant PNMA2 capsids injected into mice induce autoantibodies that preferentially bind external “spike” PNMA2 capsid epitopes, whereas a capsid-assembly-defective PNMA2 protein is not immunogenic. PNMA2 autoantibodies in cerebrospinal fluid of patients with anti-Ma2 paraneoplastic disease show similar preferential binding to spike capsid epitopes. PNMA2 capsid-injected mice develop learning and memory deficits. These observations suggest that PNMA2 capsids act as an extracellular antigen, capable of generating an autoimmune response that results in neurological deficits.

KW - autoimmune disorder

KW - capsid

KW - Gag

KW - intercellular signaling

KW - paraneoplastic disorder

KW - PNMA

KW - retrotransposon

KW - retrovirus

KW - virus

U2 - 10.1016/j.cell.2024.01.009

DO - 10.1016/j.cell.2024.01.009

M3 - Journal article

C2 - 38301645

AN - SCOPUS:85185348752

VL - 187

SP - 831-845.e19

JO - Cell

JF - Cell

SN - 0092-8674

IS - 4

ER -

ID: 384618483