Increased positive selection pressure in persistent (SSPE) versus acute measles virus infections

Area of Science:

• Virology
• Molecular Evolution
• Immunology

Background:

• Measles virus (MV) causes acute infections and persistent disease, such as subacute sclerosing panencephalitis (SSPE).
• Understanding the evolutionary pressures on MV strains is crucial for deciphering viral persistence mechanisms.

Purpose of the Study:

• To compare positive selection acting on acute and persistent measles virus strains.
• To investigate the role of selection in viral surface glycoproteins (F and H genes) and the matrix (M) gene during persistent infection.

Main Methods:

• Comparative analysis of positive selection in measles virus genes (F, H, M) from acute and SSPE cases.
• Phylogenetic inference incorporating hypermutated SSPE M gene sequences.

Main Results:

• Significantly stronger positive selection was observed in the F and H genes of SSPE strains versus acute MV.
• Positively selected sites in SSPE F and H genes are linked to structural, functional, and antigenic regions, not solely cell passaging artifacts.
• No positive selection was detected in the M gene of acute MV strains.
• The estimated molecular evolution rate for SSPE strains (3.4 x 10^-4 subs/site/year) is comparable to acute strains.

Conclusions:

• Positive selection, particularly in surface glycoproteins, plays a key role in the maintenance of measles virus persistent infections.
• These evolutionary pressures contribute to viral adaptation in the context of SSPE.
• The findings provide insights into the molecular mechanisms underlying measles virus pathogenesis and persistence.