SARS-CoV-2 Infection Associated with HHV-6A Reactivation and an Inhibitory KIR2DL2/HLA-C1 Immunogenetic Profile

Area of Science:

• Immunology
• Virology
• Genetics

Background:

• Natural killer (NK) cells regulate antiviral immunity via activating and inhibitory receptors like killer immunoglobulin-like receptors (KIRs).
• Previous studies linked increased KIR2DL2 and HLA-C1 to higher human herpesvirus (HHV) susceptibility.
• KIR-mediated NK cell function plays a role in host-virus interactions.

Purpose of the Study:

• To investigate the association between KIR2DL2/HLA-C1 genotype and human herpesvirus 6 (HHV-6) reactivation in SARS-CoV-2 infected individuals.
• To explore the potential link between this genetic profile, HHV-6 co-infection, and COVID-19 severity.

Main Methods:

• Genotyping for KIR2DL2 and HLA-C1 was performed on 110 SARS-CoV-2 positive and 109 negative subjects.
• HHV-6A/B reactivation was assessed in plasma samples using molecular methods.
• Correlation analysis was conducted between genetic profiles, viral reactivation, and clinical outcomes, including mortality and comorbidities.

Main Results:

• SARS-CoV-2 positive individuals exhibited a higher frequency of the KIR2DL2/HLA-C1 haplotype.
• Increased HHV-6A reactivation was observed in SARS-CoV-2 positive subjects.
• The co-occurrence of KIR2DL2/HLA-C1 and HHV-6A DNAemia was more prevalent in deceased and comorbid patients, particularly those with cardiovascular issues.

Conclusions:

• The KIR2DL2/HLA-C1 haplotype may enhance NK cell inhibition, promoting HHV-6A persistence and immune dysregulation in SARS-CoV-2 infection.
• This genetic and viral combination could serve as a molecular signature for predicting COVID-19 outcomes.
• Understanding these interactions is crucial for managing viral co-infections and improving patient prognosis.