Host Genetics, Innate Immune Responses, and Cellular Death Pathways in Poliomyelitis Patients.

Area of Science:

• Virology
• Immunology
• Genetics

Background:

• Poliovirus (PV) infection typically causes mild illness, but paralytic poliomyelitis (PPM) occurs rarely.
• The genetic factors influencing PV infection progression and pathogenesis remain largely unknown.

Purpose of the Study:

• To investigate the genetic basis of paralytic poliomyelitis (PPM).
• To explore the role of host genetic variations in poliovirus (PV) infection outcomes.

Main Methods:

• Whole-exome sequencing (WES) was performed on 18 patients with PPM.
• Functional analyses of peripheral blood mononuclear cells (PBMCs) and monocyte-derived macrophages (MdMs) were conducted.

Main Results:

• Rare variants were identified in host genes related to interferon signaling, viral replication, apoptosis, and autophagy.
• Patients showed a trend towards increased viral burden in MdMs, indicating reduced PV control.
• IFNβ response in MdMs correlated with viral burden in patients.

Conclusions:

• Genetic variants in innate immunity and cell death pathways likely contribute to the clinical presentation of PV infection.
• This study is the first to link genetic profiles with immune responses and viral burden in primary cells of PPM patients.