Simian hemorrhagic fever virus: Recent advances

Area of Science:

• Virology
• Molecular Biology
• Immunology

Background:

• The simian hemorrhagic fever virus (SHFV) genome possesses unique features within the Arteriviridae family, including multiple papain-like proteases and duplicated sets of minor structural proteins.
• SHFV causes severe hemorrhagic fever in macaques but asymptomatic infections in natural hosts like baboons, suggesting host-specific differences in viral pathogenesis.

Purpose of the Study:

• To investigate the functional roles of SHFV papain-like proteases (PLP1s) and minor structural proteins in viral replication.
• To compare SHFV infection dynamics and host immune responses in susceptible macaques and natural host baboons.

Main Methods:

• In vitro transcription/translation assays with wildtype and mutant SHFV polyprotein constructs to analyze protease activity and cleavage sites.
• Mass spectrometry to confirm protease cleavage sites.
• Construction of a full-length infectious SHFV cDNA clone and generation of mutant clones to assess the necessity of minor structural proteins.
• Infection of macaque and baboon macrophages and myeloid dendritic cells to compare viral replication, yields, and cytokine production.

Main Results:

• SHFV papain-like proteases (PLP1α, PLP1β, PLP1γ) were functional, with specific catalytic residues and cleavage sites identified. PLP1γ exhibited dual cleavage activity.
• All eight minor structural proteins were found to be indispensable for the production of infectious extracellular SHFV.
• SHFV replicated more efficiently in macaque cells than in baboon cells, with distinct differences in macrophage infection rates and cytokine induction (IL-1β, IL-6, IL-12/23(p40), TNF-α, MIP-1α) observed between the two species.

Conclusions:

• The study elucidates the essentiality of SHFV minor structural proteins for infectious virion assembly and release.
• Significant host-specific differences exist in SHFV replication efficiency and the induction of pro-inflammatory cytokines, contributing to the distinct disease outcomes observed in macaques and baboons.