Paired immunoglobulin-like receptor B is an entry receptor for mammalian orthoreovirus.
Pengcheng ShangJoshua D SimpsonGwen M TaylorDanica M SutherlandOlivia L WelshPavithra AravamudhanRita Dos Santos NatividadeKristina SchwabJoshua J MichelAmanda C PoholekYijen L WuDhivyaa RajasundaramMelanie KoehlerDavid AlsteensTerence S DermodyPublished in: Nature communications (2023)
Mammalian orthoreovirus (reovirus) infects most mammals and is associated with celiac disease in humans. In mice, reovirus infects the intestine and disseminates systemically to cause serotype-specific patterns of disease in the brain. To identify receptors conferring reovirus serotype-dependent neuropathogenesis, we conducted a genome-wide CRISPRa screen and identified paired immunoglobulin-like receptor B (PirB) as a receptor candidate. Ectopic expression of PirB allowed reovirus binding and infection. PirB extracelluar D3D4 region is required for reovirus attachment and infectivity. Reovirus binds to PirB with nM affinity as determined by single molecule force spectroscopy. Efficient reovirus endocytosis requires PirB signaling motifs. In inoculated mice, PirB is required for maximal replication in the brain and full neuropathogenicity of neurotropic serotype 3 (T3) reovirus. In primary cortical neurons, PirB expression contributes to T3 reovirus infectivity. Thus, PirB is an entry receptor for reovirus and contributes to T3 reovirus replication and pathogenesis in the murine brain.
Keyphrases
- single molecule
- binding protein
- genome wide
- poor prognosis
- dengue virus
- dna methylation
- celiac disease
- multiple sclerosis
- blood pressure
- gene expression
- type diabetes
- long non coding rna
- high resolution
- escherichia coli
- zika virus
- klebsiella pneumoniae
- skeletal muscle
- capillary electrophoresis
- high fat diet induced
- single cell
- mass spectrometry