Genetic defects underlying severe viral diseases

7.  Zhang Q, Bastard P, Liu Z, et al. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. Science. (2020).

Initial discovery that inborn errors of immunity affecting the type I IFN pathway could lead to severe COVID-19. Including patients with complete IFNAR1 or IFNAR2 defects.

8. Chan, Y.H.*, Z. Liu*, P. Bastard* et al., Human TMEFF1 is a restriction factor for herpes simplex virus in the brain. Nature (2024). *: co-first authors. (> 50 co-authors).

I co-discovered that TMEFF1 functions as a crucial restriction factor, inhibiting viral entry into human cortical neurons via interacting with the HSV-1 receptor NECTIN-1 on the cell surface. It is the first cell-specific viral restriction factor whose defect leads to severe viral disease in Humans.

9. P. Bastard et al., A loss-of-function IFNAR1 allele in Polynesia underlies severe viral diseases in homozygotes. J Exp Med (2022).

A common loss-of-function allele leads to seevre viral disease in homozygocity in polynesia. Clinical implications are immediate, and local colleagues have lauched a nation-wide screening program.

10. P. Bastard et al., Herpes simplex encephalitis in a patient with a distinctive form of inherited IFNAR1 deficiency. J Clin Invest (2020). (> 50 co-authors).

Herpes simplex virus encephalitis (HSE) is the most frequent sporadic viral encephalitis in the Western world. I identified and then characterized in depth a patient who had suffered from HSE and harbored a large homozygous deletion in IFNAR1 (the receptor of type I IFNs). The cells from the patient were totally unresponsive to type I IFNs and highly susceptible to viruses. These findings indicate that CNS neuron-intrinsic immunity to viruses in the forebrain is controlled by type I IFNs.