CLPTM1L is a GPI-anchoring pathway component targeted by HCMV

Inbal Kol*, Ahmed Rishiq, Mevaseret Cohen, Shira Kahlon, Ophir Pick, Liat Dassa, Natan Stein, Yotam Bar-On, Dana G. Wolf, Einat Seidel, Ofer Mandelboim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


The GPI-anchoring pathway plays important roles in normal development and immune modulation. MHC Class I Polypeptide-related Sequence A (MICA) is a stress-induced ligand, downregulated by human cytomegalovirus (HCMV) to escape immune recognition. Its most prevalent allele, MICA*008, is GPI-anchored via an uncharacterized pathway. Here, we identify cleft lip and palate transmembrane protein 1-like protein (CLPTM1L) as a GPI-anchoring pathway component and show that during infection, the HCMV protein US9 downregulates MICA*008 via CLPTM1L. We show that the expression of some GPI-anchored proteins (CD109, CD59, and MELTF)—but not others (ULBP2, ULBP3)—is CLPTM1L-dependent, and further show that like MICA*008, MELTF is downregulated by US9 via CLPTM1L during infection. Mechanistically, we suggest that CLPTM1L’s function depends on its interaction with a free form of PIG-T, normally a part of the GPI transamidase complex. We suggest that US9 inhibits this interaction and thereby downregulates the expression of CLPTM1L-dependent proteins. Altogether, we report on a new GPI-anchoring pathway component that is targeted by HCMV.

Original languageAmerican English
Article numbere202207104
JournalJournal of Cell Biology
Issue number9
StatePublished - 4 Sep 2023
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2023 Kol et al.


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