Genetic control of alphavirus pathogenesis

Area of Science:

• Virology
• Immunology
• Genetics

Background:

• Alphaviruses (family Togaviridae) are re-emerging global health threats due to expanding mosquito vector ranges.
• Alphavirus infections cause diverse diseases, including rash, arthritis, and encephalitis, with potential for long-term sequelae.
• Host genetics are recognized as a critical determinant of susceptibility and disease severity in alphavirus infections.

Purpose of the Study:

• To review current knowledge on how host genetic factors influence alphavirus pathogenesis.
• To discuss emerging technologies for understanding host-viral genetic interactions in alphavirus disease.

Main Methods:

• Review of existing literature on alphavirus natural history, experimental infections, and genetic studies.
• Analysis of genome-wide genetic screens (loss-of-function, microarrays, RNA-sequencing) and candidate gene studies.
• Focus on the role of the host immune response in alphavirus outcomes.

Main Results:

• Host genetics play a major role in determining susceptibility and clinical disease severity.
• The host immune response is a key factor influenced by host genetics in alphavirus pathogenesis.
• Long-term sequelae can occur irrespective of the specific alphavirus, highlighting the importance of host factors.

Conclusions:

• Host genetic factors are central to alphavirus pathogenesis and disease outcome.
• Further research using advanced technologies will elucidate the complex genetic interplay between hosts and alphaviruses.
• Understanding these interactions is vital for predicting and mitigating alphavirus-induced disease burdens.