AUTHOR=Liang Yuanhao , Hu Fengyu , Fan Hang , Li Linghua , Wan Zhengwei , Wang Haiying , Shui Jingwei , Zhou Yuanping , Tong Yigang , Cai Weiping , Tang Shixing 

TITLE=Difference of Intrahost Dynamics of the Second Human Pegivirus and Hepatitis C Virus in HPgV-2/HCV-Coinfected Patients

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=Volume 11 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.728415

DOI=10.3389/fcimb.2021.728415

ISSN=2235-2988

ABSTRACT=Background: The second human pegivirus (HPgV-2) and hepatitis C virus (HCV) belong to the Flaviviridae family and share some common genome features. However, the two viruses exhibit significant genetic diversity. The comparison of intra-host dynamics of HPgV-2 and HCV that mainly reflect virus-host interactions is needed to elucidate their difference of genetic diversity and the possible mechanisms. 
Methods: Intra-host single nucleotide variations (iSNVs) were identified by means of next-generation sequencing from both cross sectional and longitudinal samples from HPgV-2 and HCV co-infected patients. The levels of human cytokines are quantified in the patient before and after HCV elimination by the treatment of direct acting antivirals (DAA).
Results: Unlike HCV, the viral sequences of HPgV-2 are highly conserved among HPgV-2 infected patients. However, iSNV analysis confirmed the intra-host variation or quasispecies of HPgV-2. Almost all iSNVs of HPgV-2 did not accumulate or transmit within host over time, which may explain the highly conserved HPgV-2 consensus sequence. Intra-host variation of HPgV-2 mainly causes nucleotide transition in particular at the 3rd codon position and synonymous substitutions, indicating purifying and negative selection posed by host immune system. Cytokine data further indicate that HPgV-2 infection alone may not efficiently stimulate innate immune responses since pro-inflammatory cytokines expression dramatically decreased with elimination of HCV.
Conclusion: This study provided us new insights into the intra-host genomic variations and evolutionary dynamics of HPgV-2 as well as the impact of host immune selection and virus polymerase on virus evolution. The major difference of HPgV-2 and HCV makes HPgV-2 a new model to investigate RNA virus diversity and the mechanism of HPgV-2 polymerase in modulating virus replication.