Abstract:
:In humans, homologous to the E6-AP carboxyl terminus (HECT) and regulator of chromosome condensation 1 (RCC1)-like domain-containing protein 5 (HERC5) is an interferon-induced protein that inhibits replication of evolutionarily diverse viruses, including human immunodeficiency virus type 1 (HIV-1). To better understand the origin, evolution, and function of HERC5, we performed phylogenetic, structural, and functional analyses of the entire human small-HERC family, which includes HERC3, HERC4, HERC5, and HERC6. We demonstrated that the HERC family emerged >595 million years ago and has undergone gene duplication and gene loss events throughout its evolution. The structural topology of the RCC1-like domain and HECT domains from all HERC paralogs is highly conserved among evolutionarily diverse vertebrates despite low sequence homology. Functional analyses showed that the human small HERCs exhibit different degrees of antiviral activity toward HIV-1 and that HERC5 provides the strongest inhibition. Notably, coelacanth HERC5 inhibited simian immunodeficiency virus (SIV), but not HIV-1, particle production, suggesting that the antiviral activity of HERC5 emerged over 413 million years ago and exhibits species- and virus-specific restriction. In addition, we showed that both HERC5 and HERC6 are evolving under strong positive selection, particularly blade 1 of the RCC1-like domain, which we showed is a key determinant of antiviral activity. These studies provide insight into the origin, evolution, and biological importance of the human restriction factor HERC5 and the other HERC family members.IMPORTANCE Intrinsic immunity plays an important role as the first line of defense against viruses. Studying the origins, evolution, and functions of proteins responsible for effecting this defense will provide key information about virus-host relationships that can be exploited for future drug development. We showed that HERC5 is one such antiviral protein that belongs to an evolutionarily conserved family of HERCs with an ancient marine origin. Not all vertebrates possess all HERC members, suggesting that different HERCs emerged at different times during evolution to provide the host with a survival advantage. Consistent with this, two of the more recently emerged HERC members, HERC5 and HERC6, displayed strong signatures of having been involved in an ancient evolutionary battle with viruses. Our findings provide new insights into the evolutionary origin and function of the HERC family in vertebrate evolution, identifying HERC5 and possibly HERC6 as important effectors of intrinsic immunity in vertebrates.
journal_name
J Viroljournal_title
Journal of virologyauthors
Paparisto E,Woods MW,Coleman MD,Moghadasi SA,Kochar DS,Tom SK,Kohio HP,Gibson RM,Rohringer TJ,Hunt NR,Di Gravio EJ,Zhang JY,Tian M,Gao Y,Arts EJ,Barr SDdoi
10.1128/JVI.00528-18subject
Has Abstractpub_date
2018-06-13 00:00:00issue
13eissn
0022-538Xissn
1098-5514pii
JVI.00528-18journal_volume
92pub_type
杂志文章abstract::The morphology and development of four members of the reticuloendotheliosis virus group were studied by transmission electron microscopy. Virions of duck spleen necrosis virus, duck infectious anemia virus, chicken syncytial virus, and reticuloendotheliosis virus strain T are sperical with a diameter of approximately ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.16.4.1027-1038.1975
更新日期:1975-10-01 00:00:00
abstract::We have previously described the expression of the major nonstructural protein (NS-1) of Aleutian mink disease parvovirus (ADV) in insect cells by using a baculovirus vector (J. Christensen, T. Storgaard, B. Bloch, S. Alexandersen, and B. Aasted, J. Virol. 67:229-238, 1993). To study its biochemical properties, ADV NS...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.3.1802-1809.1995
更新日期:1995-03-01 00:00:00
abstract::Hepadnaviruses contain a relaxed circular DNA genome (RC-DNA) with discontinuities in both strands. Upon infectious entry into a host cell, this genome is converted into a covalently closed superhelical form (CCC-DNA), which later serves as the template for transcription. Here we examined whether the viral polymerase ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.8.4867-4874.1993
更新日期:1993-08-01 00:00:00
abstract::The interrelationship of viral ribonucleic acid (RNA) and protein synthesis in cells infected by Sindbis virus was investigated. When cultures were treated with puromycin early in the course of infection, the synthesis of interjacent RNA (26S) was preferentially inhibited. A similar result was obtained by shifting cel...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.4.2.117-122.1969
更新日期:1969-08-01 00:00:00
abstract::Borna disease virus infection is diagnosed by the presence of serum antibodies reactive with the major viral proteins, p40 and p23. Although p40 and p23 are unrelated in amino acid sequence structure, cross-reactive antibodies are described. Protein fragments and synthetic peptides were analyzed to characterize the sp...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.11.8133-8137.1996
更新日期:1996-11-01 00:00:00
abstract:UNLABELLED:Baculovirus DNAs are synthesized and inserted into preformed capsids to form nucleocapsids at a site in the infected cell nucleus, termed the virogenic stroma. Nucleocapsid assembly ofAutographa californicamultiple nucleopolyhedrovirus (AcMNPV) requires the major capsid protein VP39 and nine minor capsid pro...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02885-15
更新日期:2016-03-28 00:00:00
abstract::We previously reported that herpes simplex virus type 1 (HSV-1) can activate the stress-activated protein kinases (SAPKs) p38 and JNK. In the present study, we undertook a comprehensive and comparative analysis of the requirements for viral protein synthesis in the activation of JNK and p38. Infection with the UL36 mu...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.13.8348-8360.2005
更新日期:2005-07-01 00:00:00
abstract::The smallpox vaccine is the prototypic vaccine, yet the viral targets critical for vaccine-mediated protection remain unclear in humans. We have produced protein microarrays of a near-complete vaccinia proteome and used them to determine the major antigen specificities of the human humoral immune response to the small...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.18.11724-11733.2005
更新日期:2005-09-01 00:00:00
abstract::Marek's disease herpesvirus A antigen (MDHV-A) was identified as a 61,000- to 65,000-dalton glycoprotein by sodium dodecyl sulfate-polyacrylamide gel electrophoresis after immunoprecipitation from the culture medium of both [35S]methionine- and [14C]glucosamine-labeled infected cells by specific rabbit serum directed ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.45.3.1228-1234.1983
更新日期:1983-03-01 00:00:00
abstract::Protein kinase activity in general is stimulated at least 5- to 10-fold in ribosomal salt wash preparations from poliovirus-infected HeLa cells compared with those from mock-infected cells. The stimulation of kinase activity is manifested by increased phosphorylation of ribosome-associated polypeptides having approxim...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.61.6.1781-1787.1987
更新日期:1987-06-01 00:00:00
abstract::The major structural glycoprotein E2 of classical swine fever virus (CSFV) is responsible for eliciting neutralizing antibodies and conferring protective immunity. The current structural model of this protein predicts its surface-exposed region at the N terminus with a short stretch of the C-terminal residues spanning...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.24.11619-11625.2000
更新日期:2000-12-01 00:00:00
abstract::To further define the transcriptional regulation of the P38 promoter in the minute virus of mice (MVM) genome, we constructed a series of internal deletion and linker scanning mutations. The mutant P38 constructs were assayed for transcriptional activity in vitro by primer extension analysis with nuclear extracts from...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.6.3776-3783.1992
更新日期:1992-06-01 00:00:00
abstract::Monoclonal antibodies (MAbs) to human immunodeficiency virus type 1 were produced. Two antibodies reacted with the 17-kilodalton core protein (p17) of the virus and with its polyprotein precursor. To various degrees, each MAb neutralized infection by the cell-free virus. With a series of sequential overlapping hexapep...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.63.1.267-272.1989
更新日期:1989-01-01 00:00:00
abstract::Avian influenza A viruses, such as the highly pathogenic avian H5N1 viruses, sporadically enter the human population but often do not transmit between individuals. In rare cases, however, they establish a new lineage in humans. In addition to well-characterized barriers to cell entry, one major hurdle which avian viru...
journal_title:Journal of virology
pub_type: 杂志文章,评审
doi:10.1128/JVI.00980-13
更新日期:2013-07-01 00:00:00
abstract::Spumaviruses, or foamy viruses, express Gag proteins that are incompletely processed by the viral protease in cell cultures. To delineate the proteolytic cleavage sites between potential Gag subdomains, recombinant human spumaretrovirus (HSRV) Gag proteins of different lengths were expressed, purified by affinity chro...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.9.7907-7911.1999
更新日期:1999-09-01 00:00:00
abstract::Open reading frame P (ORF P), located at the 3' terminus of the 8.5-kb DNA sequence transcribed during latency and almost completely antisense to the gamma(1)34.5 gene, is naturally repressed by infected cell protein 4 (ICP4), the major herpes simplex virus 1 regulatory protein. Earlier studies on cells infected with ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.10.7750-7757.1997
更新日期:1997-10-01 00:00:00
abstract::The reticuloendotheliosis viruses (REVs), originally isolated from avian species, constitute a group of retroviruses which are more closely related to mammalian retroviruses than to other avian retroviruses. The envelope glycoproteins of members of the REV group display a striking amino acid sequence identity with a g...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.6.3448-3454.1992
更新日期:1992-06-01 00:00:00
abstract::Antibody-dependent enhancement of flavivirus infection, which except for dengue virus is without clear proof in vivo, is still under debate. Recently, postexposure immunoglobulin prophylaxis against tick-borne encephalitis virus, a flavivirus, was claimed to possibly have worsened the outcome of infection due to antib...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.4.2921-2927.1997
更新日期:1997-04-01 00:00:00
abstract::By inhibiting techniques using indirect immunofluorescence tests and indirect immunoelectron microscopy, the G(Gross) soluble antigens (GSA) in the body fluids of AKR and C58 mice, which have a high incidence of spontaneous leukemia, were classified according to the known specificity of G antigens in the murine Gross ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.10.6.1208-1219.1972
更新日期:1972-12-01 00:00:00
abstract::Long-acting antiretrovirals could provide a useful alternative to daily oral therapy for HIV-1-infected individuals. Building on a bi-specific molecule with adnectins targeting CD4 and gp41, a potential long-acting biologic, GSK3732394, was developed with three independent and synergistic modes of HIV entry inhibition...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00907-19
更新日期:2019-09-30 00:00:00
abstract::The mutational alterations in polyoma virus mutants ts-a and ts-25E which cause their large T-antigens to be thermolabile have been identified. In ts-a, a G leads to A transition at nucleotide 2193 causes the replacement of Ala (GCT) by Thr (ACT). In ts-25E, a G leads to T transversion at nucleotide 2883 causes the re...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.37.3.1094-1098.1981
更新日期:1981-03-01 00:00:00
abstract::We have examined the transcriptional utilization of the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) under differentiating conditions by using the embryonal carcinoma cell line NTERA-2. NTERA-2 cells undergo two distinct pathways of terminal differentiation, to a neuronal phenotype in respons...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.4.2268-2273.1992
更新日期:1992-04-01 00:00:00
abstract::The adenovirus major late promoter (MLP) is active during both the early and late phases of infection. During the early phase the activity of the MLP is similar to those of the other early viral promoters, but during the late phase the rate of transcription from the MLP becomes much greater by comparison. We report he...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.1.51-60.1990
更新日期:1990-01-01 00:00:00
abstract::Chronic infections with viruses such as hepatitis B virus, hepatitis C virus, and HIV constitute a major global public health problem. Studies of chronic viral infections in humans and mice show that persistent antigenic stimulation induces dysregulation of T cell responses; virus-specific T cells either undergo clona...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00942-12
更新日期:2012-09-01 00:00:00
abstract::UR2 is a newly characterized avian sarcoma virus whose genome contains a unique sequence that is not related to the sequences of other avian sarcoma virus transforming genes thus far identified. This unique sequence, termed ros, is fused to part of the viral gag gene. The product of the fused gag-ros gene of UR2 is a ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.42.1.228-236.1982
更新日期:1982-04-01 00:00:00
abstract::Wild-type Sindbis virus (SINV) strain MRE16 efficiently infects Aedes aegypti midgut epithelial cells (MEC), but laboratory-derived neurovirulent SINV strain TE/5'2J infects MEC poorly. SINV determinants for MEC infection have been localized to the E2 glycoprotein. The E2 amino acid sequences of MRE16 and TE/5'2J diff...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02060-07
更新日期:2008-03-01 00:00:00
abstract::Human immunodeficiency virus type 1 (HIV-1) nucleotide sequences encoding p24Gag and the Env C2V3 region were obtained from seven patients who were selected on the basis of having paradoxical seronegativity on a subset of HIV enzyme-linked immunosorbent assay detection kits and having atypical Western blot (immunoblot...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.9.5640-5649.1995
更新日期:1995-09-01 00:00:00
abstract::Brome mosaic virus (BMV), a member of the alphavirus-like super-family of positive-strand RNA viruses, encodes two proteins required for viral RNA replication: 1a and 2a. 1a contains m7G methyltransferase- and helicase-like domains, while 2a contains a polymerase (pol)-like core flanked by N- and C-terminal extensions...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.7.4729-4736.1996
更新日期:1996-07-01 00:00:00
abstract::The mechanism by which simian virus 40 converts the abortive adenovirus type 7 infection of monkey cells into an efficient lytic infection has been investigated. Analysis of ribonucleic acid (RNA) synthesis during unenhanced and enhanced infection of monkey cells has shown that adenovirus RNA synthesized in the aborti...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.10.2.220-227.1972
更新日期:1972-08-01 00:00:00
abstract::Since HIV-1 replication is modulated at multiple stages by host cell factors, identification and characterization of those host cell factors are expected to contribute to the development of novel anti-HIV therapeutics. Previous studies showed that a C-terminally truncated cytosolic form of cleavage and polyadenylation...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00124-13
更新日期:2013-07-01 00:00:00