Human pegivirus (HPgV) is transmitted through sexual or parenteral exposure and is common among patients receiving blood products. HPgV is associated with lower levels of human immunodeficiency virus (HIV) RNA and better survival among HIV-infected patients. This study aimed to investigate the prevalence of HPgV and determine its subtypes in HIV-infected individuals living in Istanbul, which has the highest rate of HIV infection in Türkiye. Total RNA extraction from plasma, cDNA synthesis, and nested PCR were performed for HPgV on plasma samples taken from 351 HIV-1-infected patients. The HPgV viral load was quantified on HPgV-positive samples. HPgV genotyping was performed by sequencing the corresponding amplicons. In the present study, the overall prevalence of HPgV RNA in HIV-infected patients was 27.3%. HPgV subtypes 1, 2a, and 2b were found, with subtype 2a being the most frequent (91.6%). Statistical analysis of HIV-1 viral load on HPgV viral load showed an opposing correlation between HIV-1 and HPgV loads. In conclusion, these data show that HPgV infection is common among HIV-positive individuals in Istanbul, Türkiye. Further comprehensive studies are needed to clarify both the cellular and molecular pathways of these two infections and to provide more information on the effect of HPgV on the course of the disease in HIV-infected individuals.

Anelloviridae and Human Pegivirus 1 (HPgV-1) blood burden have been postulated to behave as surrogate markers for immunosuppression in transplant recipients. Here, we assessed the potential utility plasma Torque teno virus (TTV), total Anelloviridae (TAV), and HPgV-1 load monitoring for the identification of allogeneic hematopoietic stem cell transplantation recipients (allo-HSCT) at increased risk of infectious events or acute graft versus host disease (aGvHD). In this single-center, observational study, plasma TTV DNA, TAV DNA, and HPgV-1 RNA loads were monitored in 75 nonconsecutive allo-HSCT recipients (median age, 54 years). Monitoring was conducted before at baseline or by days +30, +60, +90, +120, and +180 after transplantation. Pneumonia due to different viruses or Pneumocystis jirovecii, BK polyomavirus-associated haemorrhagic cystitis (BKPyV-HC), and Cytomegalovirus DNAemia were the infectious events considered in the current study. Kinetics of plasma TTV, TAV DNA, and HPgV-1 RNA load was comparable, with though and peak levels measured by days +30 and day +90 (+120 for HPgV-1). Forty patients (53%) developed one or more infectious events during the first 180 days after allo-HSCT, whereas 29 patients (39%) had aGvHD (grade II-IV in 18). Neither, TTV, TAV, nor HPgV-1 loads were predictive of overall infection or CMV DNAemia. A TTV DNA load cut-off ≥4.40 log10 (pretransplant) and ≥4.58 log10 (baseline) copies/mL predicted the occurrence of BKPyV-HC (sensitivity ≥89%, negative predictive value, ≥96%). TTV DNA loads ≥3.38 log10 by day +30 anticipated the occurrence of aGvHD (sensitivity, 90%; negative predictive value, 97%). Pretransplant HPgV-1 loads were significantly lower (p = 0.03) in patients who had aGvHD than in those who did not. Monitoring of TTV DNA or HPgV-1 RNA plasma levels either before or early after transplantation may be ancillary to identify allo-HSCT recipients at increased risk of BKPyV-HC or aGvHD.

Pseudorabies (PR) (also called Aujeszky\'s disease, AD) is a serious infectious disease affecting pigs and other animals worldwide. The emergence of variant strains of pseudorabies virus (PRV) since 2011 has led to PR outbreaks in China and a vaccine that antigenically more closely matches these PRV variants could represent an added value to control these infections.
The objective of this study was to develop new live attenuated and subunit vaccines against PRV variant strains. Genomic alterations of vaccine strains were based on the highly virulent SD-2017 mutant strain and gene-deleted strains SD-2017ΔgE/gI and SD-2017ΔgE/gI/TK, which constructed using homologous recombination technology. PRV gB-DCpep (Dendritic cells targeting peptide) and PorB (the outer membrane pore proteins of N. meningitidis) proteins containing gp67 protein secretion signal peptide were expressed using the baculovirus system for the preparation of subunit vaccines. We used experimental animal rabbits to test immunogenicity to evaluate the effect of the newly constructed PR vaccines.
Compared with the PRV-gB subunit vaccine and SD-2017ΔgE/gI inactivated vaccines, rabbits (n = 10) that were intramuscularly vaccinated with SD-2017ΔgE/gI/TK live attenuated vaccine and PRV-gB + PorB subunit vaccine showed significantly higher anti-PRV-specific antibodies as well as neutralizing antibodies and IFN-γ levels in serum. In addition, the SD-2017ΔgE/gI/TK live attenuated vaccine and PRV-gB + PorB subunit vaccine protected (90-100%) rabbits against homologous infection by the PRV variant strain. No obvious pathological damage was observed in these vaccinated rabbits.
The SD-2017ΔgE/gI/TK live attenuated vaccine provided 100% protection against PRV variant challenge. Interestingly, the subunit vaccines with gB protein linked to DCpep and PorB protein as adjuvant may also be a promising and effective PRV variant vaccine candidate.

Human pegivirus-1 (HPgV-1) is a so-called commensal virus for which no known associated organ disease has been found to date. Yet, it affects immune-reconstitution as previously studied in the HIV population, in whom active co-infection with HPgV-1 can modulate T and NK cell activation and differentiation leading to a protective effect against the evolution of the disease. Little is known on the effect of HPgV-1 on immune-reconstitution in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients, a patient population in which we and others have previously reported high prevalence of HPgV-1 replication. The aim of this study was to compare the immune reconstitution after allo-HSCT among HPgV-1-viremic and HPgV-1-non-viremic patients.
Within a cohort study of 40 allo-HSCT patients, 20 allo-HSCT recipients positive in plasma sample for HPgV-1 by rRT-PCR during the first year (1, 3, 6, 12 months) after transplantation were matched with 20 allo-HSCT recipients negative for HPgV-1. T and NK cell reconstitution was monitored by flow cytometry in peripheral blood samples from allo-HSCT recipients at the same time points.
We observed no significant difference in the absolute number and subsets proportions of CD4 and CD8 T cells between patient groups at any analysed timepoint. We observed a significantly higher absolute number of NK cells at 3 months among HPgV-1-viremic patients. Immunophenotypic analysis showed a significantly higher proportion of CD56bright NK cells mirrored by a reduced percentage of CD56dim NK cells in HPgV-1-positive patients during the first 6 months after allo-HSCT. At 6 months post-allo-HSCT, NK cell phenotype significantly differed depending on HPgV-1, HPgV-1-viremic patients displaying NK cells with lower CD16 and CD57 expression compared with HPgV-1-negative patients. In accordance with their less differentiated phenotype, we detected a significantly reduced expression of granzyme B in NK cells in HPgV-1-viremic patients at 6 months.
Our study shows that HPgV-1-viremic allo-HSCT recipients displayed an impaired NK cell, but not T cell, immune-reconstitution compared with HPgV-1-non-viremic patients, revealing for the first time a potential association between replication of the non-pathogenic HPgV-1 virus and immunomodulation after allo-HSCT.

Two groups identified a novel human flavivirus in the mid-1990s. One group named the virus hepatitis G virus (HGV) and the other named it GB Virus type C (GBV-C). Sequence analyses found these two isolates to be the same virus, and subsequent studies found that the virus does not cause hepatitis despite sharing genome organization with hepatitis C virus. Although HGV/GBV-C infection is common and may cause persistent infection in humans, the virus does not appear to directly cause any other known disease state. Thus, the virus was renamed \"human pegivirus 1\" (HPgV-1) for \"persistent G\" virus. HPgV-1 is found primarily in lymphocytes and not hepatocytes, and several studies found HPgV-1 infection associated with prolonged survival in people living with HIV. Co-infection of human lymphocytes with HPgV-1 and HIV inhibits HIV replication. Although three viral proteins directly inhibit HIV replication in vitro, the major effects of HPgV-1 leading to reduced HIV-related mortality appear to result from a global reduction in immune activation. HPgV-1 specifically interferes with T cell receptor signaling (TCR) by reducing proximal activation of the lymphocyte specific Src kinase LCK. Although TCR signaling is reduced, T cell activation is not abolished and with sufficient stimulus, T cell functions are enabled. Consequently, HPgV-1 is not associated with immune suppression. The HPgV-1 immunomodulatory effects are associated with beneficial outcomes in other diseases including Ebola virus infection and possibly graft-versus-host-disease following stem cell transplantation. Better understanding of HPgV-1 immune escape and mechanisms of inflammation may identify novel therapies for immune-based diseases.

Human pegivirus-1 (HPgV-1) is known for its protective role in HIV co-infected individuals. This immunomodulatory effect raised questions concerning the possible role of HPgV-1 infection and the risk of rejection in liver transplanted patients. We aimed to evaluate the possible protective effect of HPgV-1 on graft outcome of liver transplanted patients. A total of 283 patients were recruited. Formalin-fixed paraffin-embedded tissue samples were collected from the explanted liver. HBV-DNA, HCV-RNA, and HPgV-1-RNA were determined using PCR and multiplex RT-PCR assays. The clinical course of patients including the occurrence of acute cellular rejection was compared between HPgV-1-infected vs. uninfected patients. HBV-DNA, HCV-RNA and HPgV-1-RNA were detected in 42.6%, 4.9%, and 7.8% of samples, respectively. None of the HPgV-1-infected patients experienced graft rejection. Group LASSO logistic regression revealed that HPgV-1 infection was the only factor which significantly reduced the odds of graft rejection (OR = 0.5, 95% CI = 0.29-0.89). No significant association was found between the presence of HPgV-1 with HBV and HCV infections. The lack of graft rejection in HPgV-1-infected liver transplanted patients might indicate a possible role of this virus for graft surveillance. Since these are still preliminary findings, prospective studies should further elucidate the role of HPgV-1 in liver transplantation outcomes.

Human pegivirus-1 (HPgV-1) is a lymphotropic human virus, typically considered nonpathogenic, but its infection can sometimes cause persistent viremia both in immunocompetent and immunosuppressed individuals. In a viral discovery research program in hematopoietic stem cell transplant (HSCT) pediatric patients, HPgV-1 was detected in 3 out of 14 patients (21.4%) using a target enrichment next-generation sequencing method, and the presence of the viruses was confirmed by agent-specific qRT-PCR assays. For the first time in this patient cohort, complete genomes of HPgV-1 were acquired and characterized. Phylogenetic analyses indicated that two patients had HPgV-1 genotype 2 and one had HPgV-1 genotype 3. Intra-host genomic variations were described and discussed. Our results highlight the necessity to screen HSCT patients and blood and stem cell donors to reduce the potential risk of HPgV-1 transmission.

Human pegivirus 1 (HPgV-1) is a Positive-sense single-stranded RNA (+ ssRNA) virus, discovered in 1995 as a Flaviviridae member, and the closest human virus linked to HCV. In comparison to HCV, HPgV-1 seems to be lymphotropic and connected to the viral group that infects T and B lymphocytes. HPgV-1 infection is not persuasively correlated to any known human disease; nevertheless, multiple studies have reported a connection between chronic HPgV-1 infection and improved survival in HPgV-1/HIV co-infected patients with a delayed and favorable impact on HIV infection development. While the process has not been thoroughly clarified, different mechanisms for these observations have been proposed. HPgV-1 is categorized into seven genotypes and various subtypes. Infection with HPgV-1 is relatively common globally. It can be transferred parenterally, sexually, and through vertical ways, and thereby its co-infection with HIV and HCV is common. In most cases, the clearance of HPgV-1 from the body can be achieved by developing E2 antibodies after infection.
In this review, we thoroughly discuss the current knowledge and recent advances in understanding distinct epidemiological, molecular, and clinical aspects of HPgV-1.
Due to the unique characteristics of the HPgV-1, so advanced research on HPgV-1, particularly in light of HIV co-infection and other diseases, should be conducted to explore the essential mechanisms of HIV clearance and other viruses and thereby suggest novel strategies for viral therapy in the future.

Human pegivirus-1 (HPgV-1) is a member of the Flaviviridae family and the Pegivirus genus. Despite having been discovered 25 years ago, there is still much to know regarding HPgV-1 clinical impact, as this virus is currently not associated with any pathology. Yet, HPgV-1 prevalence and molecular characterization are still unknown in many countries, including Portugal. To fill in this knowledge gap, this study aimed to determine the occurrence and molecular characterization of HPgV-1 in a group of healthy blood donors from the north of Portugal. Blood samples from 465 Portuguese blood donors were collected from a major Hospital Center in the north of Portugal. RNA was extracted and an initial nested RT-PCR was performed targeting the conserved 5\'-untranslated region  region of the HPgV-1 genome. A second nested RT-PCR targeting the E2 region was performed for genotyping. Only one sample tested positive for HPgV-1 RNA, resulting in a prevalence of approximately 0.22%. Phylogenetic analyses confirmed the characterization as genotype 2, the most prevalent in Europe.

Human pegivirus (HPgV-1), previously known as GB virus C (GBV-C) or hepatitis G virus (HGV), is a single-stranded positive RNA virus belonging to the genus Pegivirus of the Flaviviridae family. It is transmitted by percutaneous injuries (PIs), contaminated blood and/or blood products, sexual contact, and vertical mother-to-child transmission. It is widely prevalent in general population, especially in high-risk groups. HPgV-1 viremia is typically cleared within the first 1-2 years of infection in most healthy individuals, but may persist for longer periods of time in immunocompromised individuals and/or those co-infected by other viruses. A large body of evidences indicate that HPgV-1 persistent infection has a beneficial clinical effect on many infectious diseases, such as acquired immunodeficiency syndrome (AIDS) and hepatitis C. The beneficial effects seem to be related to a significant reduction of immune activation, and/or the inhabitation of co-infected viruses (e.g. HIV-1). HPgV-1 has a broad cellular tropism for lymphoid and myeloid cells, and preferentially replicates in bone marrow and spleen without cytopathic effect, implying a therapeutic potential. The paper aims to summarize the natural history, prevalence and distribution characteristics, and pathogenesis of HPgV-1, and discuss its association with other human viral diseases, and potential use in therapy as a biovaccine or viral vector.