The Flaviviridae is a family of small enveloped viruses with RNA genomes of 9000-13 000 bases. Most infect mammals and birds. Many flaviviruses are host-specific and pathogenic, such as hepatitis C ...virus in the genus Hepacivirus. The majority of known members in the genus Flavivirus are arthropod borne, and many are important human and veterinary pathogens (e.g. yellow fever virus, dengue virus). This is a summary of the current International Committee on Taxonomy of Viruses (ICTV) report on the taxonomy of the Flaviviridae, which is available at www.ictv.global/report/flaviviridae.
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
, 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.
We propose the creation of seven new species in the genus Pestivirus (family Flaviviridae) in addition to the four existing species, and naming species in a host-independent manner using the format ...Pestivirus X. Only the virus species names would change; virus isolates would still be referred to by their original names. The original species would be re-designated as Pestivirus A (original designation Bovine viral diarrhea virus 1), Pestivirus B (Bovine viral diarrhea virus 2), Pestivirus C (Classical swine fever virus) and Pestivirus D (Border disease virus). The seven new species (and example isolates) would be Pestivirus E (pronghorn pestivirus), Pestivirus F (Bungowannah virus), Pestivirus G (giraffe pestivirus), Pestivirus H (Hobi-like pestivirus), Pestivirus I (Aydin-like pestivirus), Pestivirus J (rat pestivirus) and Pestivirus K (atypical porcine pestivirus). A bat-derived virus and pestiviruses identified from sheep and goat (Tunisian sheep pestiviruses), which lack complete coding region sequences, may represent two additional species.
GB virus C: the good boy virus? Bhattarai, Nirjal; Stapleton, Jack T
Trends in microbiology,
03/2012, Letnik:
20, Številka:
3
Journal Article
Recenzirano
Odprti dostop
GB virus C (GBV-C) is a lymphotropic human virus discovered in 1995 that is related to hepatitis C virus (HCV). GBV-C infection has not been convincingly associated with any disease; however, several ...studies found an association between persistent GBV-C infection and improved survival in HIV-positive individuals. GBV-C infection modestly alters T cell homeostasis in vivo through various mechanisms, including modulation of chemokine and cytokine release and receptor expression, and by diminution of T cell activation, proliferation and apoptosis, all of which may contribute to improved HIV clinical outcomes. In vitro studies confirm these clinical observations and demonstrate an anti-HIV replication effect of GBV-C. This review summarizes existing data on potential mechanisms by which GBV-C interferes with HIV, and the research needed to capitalize on this epidemiological observation.
The 2005 consensus proposal for the classification of hepatitis C virus (HCV) presented an agreed and uniform nomenclature for HCV variants and the criteria for their assignment into genotypes and ...subtypes. Since its publication, the available dataset of HCV sequences has vastly expanded through advancement in nucleotide sequencing technologies and an increasing focus on the role of HCV genetic variation in disease and treatment outcomes. The current study represents a major update to the previous consensus HCV classification, incorporating additional sequence information derived from over 1,300 (near‐)complete genome sequences of HCV available on public databases in May 2013. Analysis resolved several nomenclature conflicts between genotype designations and using consensus criteria created a classification of HCV into seven confirmed genotypes and 67 subtypes. There are 21 additional complete coding region sequences of unassigned subtype. The study additionally describes the development of a Web resource hosted by the International Committee for Taxonomy of Viruses (ICTV) that maintains and regularly updates tables of reference isolates, accession numbers, and annotated alignments (http://talk.ictvonline.org/links/hcv/hcv-classification.htm). The Flaviviridae Study Group urges those who need to check or propose new genotypes or subtypes of HCV to contact the Study Group in advance of publication to avoid nomenclature conflicts appearing in the literature. While the criteria for assigning genotypes and subtypes remain unchanged from previous consensus proposals, changes are proposed in the assignment of provisional subtypes, subtype numbering beyond “w,” and the nomenclature of intergenotypic recombinant. Conclusion: This study represents an important reference point for the consensus classification of HCV variants that will be of value to researchers working in clinical and basic science fields. (Hepatology 2014;59:318‐327)
Proposals are described for the assignment of recently reported viruses, infecting rodents, bats and other mammalian species, to new species within the Hepacivirus and Pegivirus genera (family ...Flaviviridae). Assignments into 14 Hepacivirus species (Hepacivirus A-N) and 11 Pegivirus species (Pegivirus A-K) are based on phylogenetic relationships and sequence distances between conserved regions extracted from complete coding sequences for members of each proposed taxon. We propose that the species Hepatitis C virus is renamed Hepacivirus C in order to acknowledge its unique historical position and so as to minimize confusion. Despite the newly documented genetic diversity of hepaciviruses and pegiviruses, members of these genera remain phylogenetically distinct, and differ in hepatotropism and the possession of a basic core protein; pegiviruses in general lack these features. However, other characteristics that were originally used to support their division into separate genera are no longer definitive; there is overlap between the two genera in the type of internal ribosomal entry site and the presence of miR-122 sites in the 5' UTR, the predicted number of N-linked glycosylation sites in the envelope E1 and E2 proteins, the presence of poly U tracts in the 3' UTR and the propensity of viruses to establish a persistent infection. While all classified hepaciviruses and pegiviruses have mammalian hosts, the recent description of a hepaci-/pegi-like virus from a shark and the likely existence of further homologues in other non-mammalian species indicate that further species or genera remain to be defined in the future.
The terms extracellular vesicles, microvesicles, oncosomes, or exosomes are often used interchangeably as descriptors of particles that are released from cells and comprise a lipid membrane that ...encapsulates nucleic acids and proteins. Although these entities are defined based on a specific size range and/or mechanism of release, the terminology is often ambiguous. Nevertheless, these vesicles are increasingly recognized as important modulators of intercellular communication. The generic characterization of extracellular vesicles could also be used as a descriptor of enveloped viruses, highlighting the fact that extracellular vesicles and enveloped viruses are similar in both composition and function. Their high degree of similarity makes differentiating between vesicles and enveloped viruses in biological specimens particularly difficult. Because viral particles and extracellular vesicles are produced simultaneously in infected cells, it is necessary to separate these populations to understand their independent functions. We summarize current understanding of the similarities and differences of extracellular vesicles, which henceforth we will refer to as exosomes, and the enveloped retrovirus, HIV-1. Here, we focus on the presence of these particles in semen, as these are of particular importance during HIV-1 sexual transmission. While there is overlap in the terminology and physical qualities between HIV-1 virions and exosomes, these two types of intercellular vehicles may differ depending on the bio-fluid source. Recent data have demonstrated that exosomes from human semen serve as regulators of HIV-1 infection that may contribute to the remarkably low risk of infection per sexual exposure.
Primary analyses of a study in young women aged 16–26 years showed efficacy of the nine-valent human papillomavirus (9vHPV; HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58) vaccine against infections and ...disease related to HPV 31, 33, 45, 52, and 58, and non-inferior HPV 6, 11, 16, and 18 antibody responses when compared with quadrivalent HPV (qHPV; HPV 6, 11, 16, and 18) vaccine. We aimed to report efficacy of the 9vHPV vaccine for up to 6 years following first administration and antibody responses over 5 years.
We undertook this randomised, double-blind, efficacy, immunogenicity, and safety study of the 9vHPV vaccine study at 105 study sites in 18 countries. Women aged 16–26 years old who were healthy, with no history of abnormal cervical cytology, no previous abnormal cervical biopsy results, and no more than four lifetime sexual partners were randomly assigned (1:1) by central randomisation and block sizes of 2 and 2 to receive three intramuscular injections over 6 months of 9vHPV or qHPV (control) vaccine. All participants, study investigators, and study site personnel, laboratory staff, members of the sponsor's study team, and members of the adjudication pathology panel were masked to vaccination groups. The primary outcomes were incidence of high-grade cervical disease (cervical intraepithelial neoplasia grade 2 or 3, adenocarcinoma in situ, invasive cervical carcinoma), vulvar disease (vulvar intraepithelial neoplasia grade 2/3, vulvar cancer), and vaginal disease (vaginal intraepithelial neoplasia grade 2/3, vaginal cancer) related to HPV 31, 33, 45, 52, and 58 and non-inferiority (excluding a decrease of 1·5 times) of anti-HPV 6, 11, 16, and 18 geometric mean titres (GMT). Tissue samples were adjudicated for histopathology diagnosis and tested for HPV DNA. Serum antibody responses were assessed by competitive Luminex immunoassay. The primary evaluation of efficacy was a superiority analysis in the per-protocol efficacy population, supportive efficacy was analysed in the modified intention-to-treat population, and the primary evaluation of immunogenicity was a non-inferiority analysis. The trial is registered with ClinicalTrials.gov, number NCT00543543.
Between Sept 26, 2007, and Dec 18, 2009, we recruited and randomly assigned 14 215 participants to receive 9vHPV (n=7106) or qHPV (n=7109) vaccine. In the per-protocol population, the incidence of high-grade cervical, vulvar and vaginal disease related to HPV 31, 33, 45, 52, and 58 was 0·5 cases per 10 000 person-years in the 9vHPV and 19·0 cases per 10 000 person-years in the qHPV groups, representing 97·4% efficacy (95% CI 85·0–99·9). HPV 6, 11, 16, and 18 GMTs were non-inferior in the 9vHPV versus qHPV group from month 1 to 3 years after vaccination. No clinically meaningful differences in serious adverse events were noted between the study groups. 11 participants died during the study follow-up period (six in the 9vHPV vaccine group and five in the qHPV vaccine group); none of the deaths were considered vaccine-related.
The 9vHPV vaccine prevents infection, cytological abnormalities, high-grade lesions, and cervical procedures related to HPV 31, 33, 45, 52, and 58. Both the 9vHPV vaccine and qHPV vaccine had a similar immunogenicity profile with respect to HPV 6, 11, 16, and 18. Vaccine efficacy was sustained for up to 6 years. The 9vHPV vaccine could potentially provide broader coverage and prevent 90% of cervical cancer cases worldwide.
Merck & Co, Inc.
Human pegivirus (HPgV; originally called GB virus C/hepatitis G virus) is an RNA virus within the genus Pegivirus of the family Flaviviridae that commonly causes persistent infection. Worldwide, ~750 ...million people are actively infected (viraemic) and an estimated 0.75-1.5 billion people have evidence of prior HPgV infection. No causal association between HPgV and disease has been identified; however, several studies described a beneficial relationship between persistent HPgV infection and survival in individuals infected with human immunodeficiency virus. The beneficial effect appeared to be related to a reduction in host immune activation. HPgV replicates well in vivo (mean plasma viral loads typically >1×107 genome copies ml-1); however, the virus grows poorly in vitro and systems to study this virus are limited. Consequently, mechanisms of viral persistence and host immune modulation remain poorly characterized, and the primary permissive cell type(s) has not yet been identified. HPgV RNA is found in liver, spleen, bone marrow and PBMCs, including T- and B-lymphocytes, NK-cells, and monocytes, although the mechanism of cell-to-cell transmission is unclear. HPgV RNA is also present in serum microvesicles with properties of exosomes. These microvesicles are able to transmit viral RNA to PBMCs in vitro, resulting in productive infection. This review summarizes existing data on HPgV cellular tropism and the effect of HPgV on immune activation in various PBMCs, and discusses how this may influence viral persistence. We conclude that an increased understanding of HPgV replication and immune modulation may provide insights into persistent RNA viral infection of humans.