CT135 Mediates the Resistance of to Primate Interferon Gamma Stimulated Immune Defenses

Overview

Journal iScience

Publisher Cell Press

Date 2024 Jul 1

PMID 38947519

Authors

Mark C Fernandez

Yvonne Cosgrove Sweeney

Robert J Suchland

Steven J Carrell

Olusegun O Soge

Isabelle Q Phan

Daniel D Rockey

Dorothy L Patton

Kevin Hybiske

Affiliations

Soon will be listed here.

Abstract

Evading host innate immune defenses is a critical feature of infections, and the mechanisms used by to subvert these pathways are incompletely understood. We screened a library of chimeric mutants for genetic factors important for interference with cell-autonomous immune defenses. Mutant strains with predicted truncations of the inclusion membrane protein CT135 were susceptible to interferon gamma-activated immunity in human cells. CT135 functions to prevent host-driven recruitment of ubiquitin and p62/SQSTM to the inclusion membrane. In a nonhuman primate model of infection, a CT135-deficient strain was rapidly cleared, highlighting the importance of this virulence factor for pathogenesis. Analysis of CT135 phenotypes in primary macaque cells revealed that cell-autonomous immune defenses against are conserved between humans and nonhuman primates and connects mechanistic findings with infection outcomes.

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