Increased growth ability and pathogenicity of American- and Pacific-subtype Zika virus (ZIKV) strains compared with a Southeast Asian-subtype ZIKV strain.

We investigated the growth properties and virulence in mice of three Zika virus (ZIKV) strains of Asian/American lineage, PRVABC59, ZIKV/Hu/Chiba/S36/2016 (ChibaS36), and ZIKV/Hu/NIID123/2016 (NIID123), belonging to the three distinct subtypes of this lineage. The American-subtype strain, PRVABC59, showed the highest growth potential in vitro, whereas the Southeast Asian-subtype strain, NIID123, showed the lowest proliferative capacity. Moreover, PRVABC59- and NIID123-infected mice showed the highest and lowest viremia levels and infectious virus levels in the testis, respectively, and the rate of damaged testis in PRVABC59-infected mice was higher than in mice infected with the other two strains. Lastly, ZIKV NS1 antigen was detected in the damaged testes of mice infected with PRVABC59 and the Pacific-subtype strain, ChibaS36, at 2 weeks post-inoculation and in the epididymides of PRVABC59-infected mice at 6 weeks post-inoculation. Our results indicate that PRVABC59 and ChibaS36 exhibit increased abilities to grow in vitro and in vivo and to induce testis damage in mice. Author summary Zika virus (ZIKV) is classified into two lineages, African and Asian/American. Phylogenetic analyses have revealed that Asian/American-lineage ZIKV strains can be divided into three distinct subtypes, the American, Pacific, and Southeast Asian subtypes, presenting several amino acid differences. In this study, we examined the in vitro and in vivo growth of three Asian/American lineage ZIKV strains belonging to the three subtypes. The American-subtype strain and the Southeast Asian-subtype strain exhibited the highest and lowest growth potential in vitro, respectively, and mice infected with these ZIKV strains also showed the highest and lowest viremia levels and infectious virus levels in the testis. Moreover, the rate and extent of testis damage were highest in mice infected with the American-subtype strain. Our results indicate that the American-subtype and Pacific-subtype strains exhibit increased ability to grow in vitro and in vivo and to induce testis damage in mice.