Abstract:
:Misfolded alpha-synuclein (αS) may exhibit a number of characteristics similar to those of the prion protein, including the apparent ability to spread along neuroanatomical connections. The demonstration for this mechanism of spread is largely based on the intracerebral injections of preaggregated αS seeds in mice, in which it cannot be excluded that diffuse, surgical perturbations and hematogenous spread also contribute to the propagation of pathology. For this reason, we have utilized the sciatic nerve as a route of injection to force the inoculum into the lumbar spinal cord and induce a localized site for the onset of αS inclusion pathology. Our results demonstrate that mouse αS fibrils (fibs) injected unilaterally in the sciatic nerve are efficient in inducing pathology and the onset of paralytic symptoms in both the M83 and M20 lines of αS transgenic mice. In addition, a spatiotemporal study of these injections revealed a predictable spread of pathology to brain regions whose axons synapse directly on ventral motor neurons in the spinal cord, strongly supporting axonal transport as a mechanism of spread of the αS inducing, or seeding, factor. We also revealed a relatively decreased efficiency for human αS fibs containing the E46K mutation to induce disease via this injection paradigm, supportive of recent studies demonstrating a diminished ability of this mutant αS to undergo aggregate induction. These results further demonstrate prion-like properties for αS by the ability for a progression and spread of αS inclusion pathology along neuroanatomical connections.IMPORTANCE The accumulation of alpha-synuclein (αS) inclusions is a hallmark feature of Parkinson's disease (PD) and PD-related diseases. Recently, a number of studies have demonstrated similarities between the prion protein and αS, including its ability to spread along neuroanatomical tracts throughout the central nervous system (CNS). However, there are caveats in each of these studies in which the injection routes used had the potential to result in a widespread dissemination of the αS-containing inocula, making it difficult to precisely define the mechanisms of spread. In this study, we assessed the spread of pathology following a localized induction of αS inclusions in the lumbar spinal cord following a unilateral injection in the sciatic nerve. Using this paradigm, we demonstrated the ability for αS inclusion spread and/or induction along neuroanatomical tracts within the CNS of two αS-overexpressing mouse models.
journal_name
J Viroljournal_title
Journal of virologyauthors
Ayers JI,Riffe CJ,Sorrentino ZA,Diamond J,Fagerli E,Brooks M,Galaleldeen A,Hart PJ,Giasson BIdoi
10.1128/JVI.00586-18subject
Has Abstractpub_date
2018-08-29 00:00:00issue
18eissn
0022-538Xissn
1098-5514pii
JVI.00586-18journal_volume
92pub_type
杂志文章abstract::The J-F intercistronic region of the genomes of bacteriophages phi X174 and G4 is transcribed but not translated. It contains the potential for a perfectly base-paired hairpin structure, which has been proposed to act as a terminator of transcription or as a regulatory region for mRNA turnover (or both). We measured p...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.48.1.180-185.1983
更新日期:1983-10-01 00:00:00
abstract::Equine infectious anemia virus (EIAV) is an equine lentivirus similar to HIV-1, targets host immune cells, and causes a life-long infection in horses. The Chinese live EIAV vaccine is attenuated from long-term passaging of a highly virulent strain in vitro The parent pathogenic strain (EIAVDLV34) induces a host inflam...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00653-19
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.7.6.749-752.1971
更新日期:1971-06-01 00:00:00
abstract::The DNase/alkaline exonuclease (AE) genes are well conserved in all herpesvirus families, but recent studies have shown that the AE proteins of gammaherpesviruses such as Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) exhibit an additional function which shuts down host protein synthesis. ...
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.11.8522-8530.1997
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pub_type: 杂志文章
doi:10.1128/jvi.76.23.11880-11888.2002
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abstract::TRIM5α is a natural resistance factor that binds retroviral capsid proteins and restricts virus replication. The B30.2/SPRY domain of TRIM5α is polymorphic in rhesus macaques, and some alleles are associated with reduced simian immunodeficiency virus (SIV) SIV(mac251) and SIV(smE543) replication in vivo. We determined...
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journal_title:Journal of virology
pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.63.4.1833-1838.1989
更新日期:1989-04-01 00:00:00
abstract::The administration of cyclophosphamide (50 to 100 mg/kg) at 48 to 72 h before removal of murine lung or spleen mononuclear cells for culture rendered DBA/2 mice incapable of generating an effective cytotoxic T-lymphocyte response to influenza A virus-infected cells. The cytotoxic T-lymphocyte precursor frequency to in...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.51.1.20-25.1984
更新日期:1984-07-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.80.8.4147-4156.2006
更新日期:2006-04-01 00:00:00
abstract::JC virus (JCV), along with other members of the polyomavirus family, encodes a class of highly conserved proteins, T antigens, that are capable of inducing aneuploidy in cultured cells. We have previously isolated T-antigen DNA variants of JCV from both colon cancer tissues and the corresponding nonneoplastic gastroin...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.4.1996-2001.2001
更新日期:2001-02-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.53.1.120-127.1985
更新日期:1985-01-01 00:00:00
abstract::A monoclonal antibody, MAb vpg15, inhibits feline immunodeficiency virus (FIV) infection in tissue culture. The antibody is directed to a determinant of the feline cell surface marker, CD9, implying that CD9 may serve as a viral receptor or coreceptor in this system. In cells expressing CD9, MAb vpg15 markedly delayed...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.8.5742-5749.1997
更新日期:1997-08-01 00:00:00
abstract::Autographa californica nuclear polyhedrosis virus late and very late mRNAs are transcribed by an RNA polymerase consisting of four virus-encoded polypeptides: LEF-8, LEF-9, LEF-4, and p47. The 464-amino-acid LEF-4 subunit contains the signature motifs of GTP:RNA guanylyltransferases (capping enzymes). Here, we show th...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.12.10020-10028.1998
更新日期:1998-12-01 00:00:00
abstract::The NS3 protein of hepatitis C virus (HCV) possesses protease activity responsible for the proteolytic cleavage of the viral polyprotein at the junctions of nonstructural proteins downstream of NS3. The NS3 protein was also found to be internally cleaved. In this study, we demonstrated that internal cleavages occurred...
journal_title:Journal of virology
pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:2003-10-01 00:00:00
abstract::Equine infectious anemia virus (EIAV) provides a natural model system by which immunological control of lentivirus infections may be studied. To date, no detailed study addressing in parallel both the humoral and cellular immune responses induced in horses upon infection by EIAV has been conducted. Therefore, we initi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.5.3840-3852.1997
更新日期:1997-05-01 00:00:00
abstract::The putative envelope 2 (E2) gene of hepatitis C virus (HCV) contains a highly variable region referred to as hypervariable region 1 (HVR1). We hypothesized that this genetic variability is driven by immune selection pressure, rather than representing the accumulation of random mutations in a region with relatively li...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.7.3058-3066.2000
更新日期:2000-04-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:2016-06-10 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.18.3.1143-1146.1976
更新日期:1976-06-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.2.757-766.1990
更新日期:1990-02-01 00:00:00
abstract::The assembly of an orthoretrovirus such as HIV-1 requires the coordinated functioning of multiple biochemical activities of the viral Gag protein. These activities include membrane targeting, lattice formation, packaging of the RNA genome, and recruitment of cellular cofactors that modulate assembly. In most previous ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01844-19
更新日期:2020-02-14 00:00:00
abstract::A fragment of chicken DNA containing the left long terminal repeat of endogenous retrovirus ev-2 and flanking cellular sequences has been molecularly cloned and analyzed. Comparison with sequence data from the analogous regions of ev-1 and Rous-associated virus-0 viral DNA reveals similarities among flanking regions o...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.45.2.868-871.1983
更新日期:1983-02-01 00:00:00
abstract::Bats have been identified as the natural reservoir of severe acute respiratory syndrome (SARS)-like and SARS coronaviruses (SLCoV and SCoV). However, previous studies suggested that none of the currently sampled bat SLCoVs is the descendant of the direct ancestor of SCoV, based on their relatively distant phylogenetic...
journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:2008-02-01 00:00:00