Heat increased the editing efficiency of human papillomavirus E 2 gene by inducing upregulation of APOBEC 3 A and 3 G

Apolipoprotein B mRNA-editing catalytic polypeptide (APOBEC) 3 proteins have been identified as potent viral DNA mutators and have broad antiviral activity. In this study, we demonstrated APOBEC3A (A3A) and A3G expression levels were significantly upregulated in HPV infected cell lines and tissues. Heat treatment resulted in elevated expression of A3A and A3G in a temperature-dependent manner in HPV infected cells. Correspondingly, 44 oC heating treated HPV infected cells showed accumulated G-to-A or C-to-T mutation in HPVE2 gene. Knockdown of A3A or A3G could promote cell viability, along with the lower frequency of A/T in HPV E2 gene. In addition, regressing genital viral warts also harbored high G-to-A or C-to-T mutation in HPVE2 gene. Taken together, we demonstrate that APOBEC3 expression and editing function was heat sensitive to a certain degree, partly explaining the mechanism of action of local hyperthermia to treat viral warts.