Disclosed are compositions and methods for increasing virus production. In particular, disclosed herein are cell or cell line comprises reduced expression of one or more cellular genes selected from the group comprising COQ9, FGF2, NAT9, NDUFA9, NEU2, PLA2G1B, PYCR1, RAD51AP1, STRADA, SVOPL, and/or ZFYVE9 for use in increasing viral production.

Disclosed herein are a duck hepatitis A virus type 3 (DHAV-3) mutant CH-P60-117C and a construction method thereof. The DHAV-3 mutant CH-P60-117C is constructed by mutating A at position 117 of 5′-UTR of the genome of the DHAV-3 virulent strain to C; mutating T at position 1142 to A to mutate tyrosine-164 of VP0 protein of the parent strain to asparagine; and mutating C at position 4334 to A so that leucine-71 of the viral protein 2C of the parent strain is mutated to isoleucine.

Disclosed herein are a duck hepatitis A virus type 3 (DHAV-3) mutant CH-P60-117C and a construction method thereof. The DHAV-3 mutant CH-P60-117C is constructed by mutating A at position 117 of 5-UTR of the genome of the DHAV-3 virulent strain to C; mutating T at position 1142 to A to mutate tyrosine-164 of VP0 protein of the parent strain to asparagine; and mutating C at position 4334 to A so that leucine-71 of the viral protein 2C of the parent strain is mutated to isoleucine.

Disclosed are compositions and methods for increasing virus production.

A method of culturing wild-type hepatitis A virus (wtHAV) using induced differentiated pluripotent stem cell-derived hepatocytes. Specifically, iPSCs were used to differentiate into definitive endodermal (DE) cell, and then the DE cells were differentiated into four stages of hepatocyte progenitor (HpSC), hepatoblasts (HB), immature hepatocytes (immHep), and derived hepatocytes (dHep), and each stage cells were inoculated with wtHAV, and it was confirmed that all cells could be cultured more than the initial inoculation amount and the culture reproducibility. In addition, it was confirmed that the differentiated cells of each stage of the present invention can function as sufficient infection hosts, as the number of HAV gene copies increased after 3 days after inoculation. And thus, by inoculating HAV at each stage of differentiation and selecting the optimal time point of culture, it is possible to shorten the culture period and establish an efficient culture system with optimal effect.