Figure 3.

Bidirectional regulation of m⁶A modification in viral infection. This image compares the differential regulatory roles of SFTSV in host RNA epitranscriptomic modifications and viral replication in the context of mutational backgrounds at the A273 site versus the A63/A343 sites. The left panel illustrates that at the A273 site, the viral nucleocapsid protein (Np) interacts with the host methyltransferase complex METTL3/METTL14 to promote the m⁶A modification of viral RNAs. The m⁶A-modified viral RNAs are subsequently recognized and bound by reader proteins such as YTHDF1/2/3 and IGF2BP1/2/3. This process significantly enhances RNA stability and translational efficiency, thereby promoting viral protein synthesis and viral replication. The right panel reveals that at the A63 and A343 sites, viral infection induces lactic acidification and alters the lysine lactylation (Kla) levels of host proteins, which directly affects the modification status of YTHDF1 and its ability to recognize m⁶A-marked RNAs. Meanwhile, Sirt6 is involved in removing the lactylation marks, a regulatory process that is also modulated by the viral NSs protein. Collectively, these alterations decrease viral mRNA stability and suppress related post-transcriptional regulation. This suggests that variations at distinct sites can alter SFTSV replication efficiency and the pathogenic process by modulating m⁶A recognition, RNA fate, and host translational regulatory networks.