Review of human pegivirus: Prevalence, transmission, pathogenesis, and clinical implication

Figures & data

Figure 1. Phylogenetic relationship of pegivirus. The phylogenetic tree was constructed based on RdRp gene sequences of selected Flaviviridae members using the maximum-likelihood (ML) method (MEGA 7.0.26). Four genera are classified in the Flaviviridae family. The main hosts of these viruses are also shown in the figure. The red branches highlight the members of the genus Pegivirus.

Figure 2. Genome organization of HPgV-1 and HCV. The genome encodes a single pre-polyprotein that is cleaved into mature viral proteins after co-translation and post-translation. Compared to HCV, HPgV-1 genome encodes two additional predicted proteins (protein X at upstream of E1, and protein p* between E2 and NS2), but does not encode a core protein that is an RNA-binding protein and forms the virion nucleocapsid.

Table 1. HPgV-1 proteins and their functions

Protein	Function
E1	Envelope glycoproteins
E2	Envelope glycoproteins, receptor binding
p7-like	Similar in size to HCV p7
NS2	Component of the NS2-3 protease, mediating cleavage at the NS2/NS3 junction
NS3	Protease, mediating the cleavage of NS proteins, C-terminal NTPase and helicase
NS4A	Cofactor for NS3-mediated cleavages of NS proteins
NS4B	Membrane alteration inducer
NS5A	Multifunctional phosphoprotein
NS5B	RNA-dependent RNA polymerase, genomic RNA replication

Note: The functions of some HPgV-1 proteins are predicted according to their counterparts in HCV.

Figure 3. Global prevalence and distribution of HPgV-1. BD: blood donors; HR: high-risk population mainly including IDUs, CSWs, and MSM.

Table 2. HPgV-1 prevalence in persons co-infected with HIV-1 or HCV or EBOV and clinical outcomes

HPgV-1 co-infected cohorts	HPgV-1 prevalence	Clinical outcomes
HIV-1 infected	5−47.9%	Higher survival, CD4 cell counts, and CD4+/CD8+ ratio Lower HIV-1 viral loads, and T-cell activation Slower progression to AIDS Decreased levels of cytokines and chemokines Down-regulation of CCR5 and CXCR4 expression Improved response to HAART Superior quality of life
HIV-1/HCV co-infected^a	11.8−37.2%	Reduction in cirrhosis, hepatic fibrosis and inflammation Down-regulation of LCK and DOK2 expression Lower ALT and AST levels
EBOV infected	26.5% ^b	Higher survival

a: HPgV-1 infection does not show significant beneficial effect for HCV-mono-infected individuals. Furthermore, the data and clinical findings are mostly based on patients with HIV-1/HCV/HPgV-1 triple co-infection.

b: Data from one report.

Data Availability Statement

Data sharing is not applicable to this article as no new data were created or analyzed in this study.