FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / PLoS One / The ubiquitin proteasome system plays a role in venezuelan e...
PloS one2015; 10(4); e0124792; doi: 10.1371/journal.pone.0124792

The ubiquitin proteasome system plays a role in venezuelan equine encephalitis virus infection.

Abstract: Many viruses have been implicated in utilizing or modulating the Ubiquitin Proteasome System (UPS) to enhance viral multiplication and/or to sustain a persistent infection. The mosquito-borne Venezuelan equine encephalitis virus (VEEV) belongs to the Togaviridae family and is an important biodefense pathogen and select agent. There are currently no approved vaccines or therapies for VEEV infections; therefore, it is imperative to identify novel targets for therapeutic development. We hypothesized that a functional UPS is required for efficient VEEV multiplication. We have shown that at non-toxic concentrations Bortezomib, a FDA-approved inhibitor of the proteasome, proved to be a potent inhibitor of VEEV multiplication in the human astrocytoma cell line U87MG. Bortezomib inhibited the virulent Trinidad donkey (TrD) strain and the attenuated TC-83 strain of VEEV. Additional studies with virulent strains of Eastern equine encephalitis virus (EEEV) and Western equine encephalitis virus (WEEV) demonstrated that Bortezomib is a broad spectrum inhibitor of the New World alphaviruses. Time-of-addition assays showed that Bortezomib was an effective inhibitor of viral multiplication even when the drug was introduced many hours post exposure to the virus. Mass spectrometry analyses indicated that the VEEV capsid protein is ubiquitinated in infected cells, which was validated by confocal microscopy and immunoprecipitation assays. Subsequent studies revealed that capsid is ubiquitinated on K48 during early stages of infection which was affected by Bortezomib treatment. This study will aid future investigations in identifying host proteins as potential broad spectrum therapeutic targets for treating alphavirus infections.
Get Full Text
Publication Date: 2015-04-30 PubMed ID: 25927990PubMed Central: PMC4415917DOI: 10.1371/journal.pone.0124792Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research demonstrates that the Ubiquitin Proteasome System (UPS), a protein degradation mechanism, plays a significant role in Venezuelan equine encephalitis virus (VEEV) infection and that Bortezomib, a proteasome inhibitor, can effectively suppress this virus, offering a potential therapeutic avenue for treating VEEV infections.

Role of the Ubiquitin Proteasome System (UPS) in Viral Infections

  • The researchers hypothesize that a functional UPS is necessary for efficient VEEV proliferation. This hypothesis is based on prior observations where many viruses are seen to use or modify the UPS to bolster their multiplication and maintain a persistent infection.

VEEV and the Potential of Bortezomib for Treatment

  • VEEV, an important biodefense pathogen carried by mosquitoes, is currently without a vaccine or specific treatments. This makes the identification of new therapeutic targets crucial.
  • The researchers found that at non-toxic concentrations, Bortezomib, a Food and Drug Administration (FDA) approved proteasome inhibitor, became a potent inhibitor of VEEV multiplication in a human astrocytoma cell line.
  • Bortezomib was effective against both the virulent Trinidad donkey strain and the milder TC-83 strain of VEEV. This was further affirmed by observation of its effectiveness against other New World alphaviruses such as Eastern equine encephalitis virus (EEEV) and Western equine encephalitis virus (WEEV).

Insights into VEEV’s Modulation of UPS

  • Through time-of-addition assays, it was observed that Bortezomib remained effective even when introduced several hours post-exposure to the virus, indicating the prolonged vulnerability of the viral process to proteasome inhibition.
  • Mass spectrometry analyses, confocal microscopy, and immunoprecipitation assays revealed that VEEV capsid protein (the protein shell of the virus) is ubiquitinated in infected cells, indicating one mechanism how the virus might be utilizing the UPS.
  • In early stages of infection, the capsid is ubiquitinated on Localization K48, which is affected by Bortezomib treatment suggesting further how Bortezomib could constrain VEEV.

Applications of the Research

  • This research provides crucial insights on how viruses might hijack the UPS for their multiplication and survival advantage.
  • Furthermore, the demonstrated efficacy of Bortezomib provides a new therapeutic target for not only VEEV but also for a broader spectrum of alphaviruses.
  • The findings will also aid in identifying host proteins that could potentially be broad therapeutic targets for alphavirus infections.

Cite This Article

APA
Amaya M, Keck F, Lindquist M, Voss K, Scavone L, Kehn-Hall K, Roberts B, Bailey C, Schmaljohn C, Narayanan A. (2015). The ubiquitin proteasome system plays a role in venezuelan equine encephalitis virus infection. PLoS One, 10(4), e0124792. https://doi.org/10.1371/journal.pone.0124792

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 10
Issue: 4
Pages: e0124792
PII: e0124792

Researcher Affiliations

Amaya, Moushimi
  • National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, Manassas, United States of America.
Keck, Forrest
  • National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, Manassas, United States of America.
Lindquist, Michael
  • United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, United States of America.
Voss, Kelsey
  • National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, Manassas, United States of America.
Scavone, Lauren
  • National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, Manassas, United States of America.
Kehn-Hall, Kylene
  • National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, Manassas, United States of America.
Roberts, Brian
  • Leidos Health Life Sciences, Frederick, Maryland, United States of America.
Bailey, Charles
  • National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, Manassas, United States of America.
Schmaljohn, Connie
  • United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, United States of America.
Narayanan, Aarthi
  • National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, Manassas, United States of America.

MeSH Terms

  • Animals
  • Blotting, Western
  • Bortezomib / pharmacology
  • Cell Survival / drug effects
  • Encephalitis Virus, Venezuelan Equine / drug effects
  • Encephalitis Virus, Venezuelan Equine / pathogenicity
  • Encephalomyelitis, Venezuelan Equine / metabolism
  • Guinea Pigs
  • Immunoprecipitation
  • In Situ Hybridization, Fluorescence
  • Proteasome Endopeptidase Complex / metabolism
  • Tandem Mass Spectrometry
  • Ubiquitin / metabolism

Conflict of Interest Statement

Leidos has been affiliated with this research by providing partial financial support to the completion of this project. Leidos had no impact on the design of experiments and execution, interpretation and representation of results. This collaboration does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

References

This article includes 43 references
  1. Jackson G, Einsele H, Moreau P, Miguel JS. Bortezomib, a novel proteasome inhibitor, in the treatment of hematologic malignancies.. Cancer Treat Rev 2005 Dec;31(8):591-602.
    pubmed: 16298074doi: 10.1016/j.ctrv.2005.10.001google scholar: lookup
  2. Meng L, Mohan R, Kwok BH, Elofsson M, Sin N, Crews CM. Epoxomicin, a potent and selective proteasome inhibitor, exhibits in vivo antiinflammatory activity.. Proc Natl Acad Sci U S A 1999 Aug 31;96(18):10403-8.
    pmc: PMC17900pubmed: 10468620doi: 10.1073/pnas.96.18.10403google scholar: lookup
  3. Satheshkumar PS, Anton LC, Sanz P, Moss B. Inhibition of the ubiquitin-proteasome system prevents vaccinia virus DNA replication and expression of intermediate and late genes.. J Virol 2009 Mar;83(6):2469-79.
    doi: 10.1128/JVI.01986-08pmc: PMC2648259pubmed: 19129442google scholar: lookup
  4. Curran MP, McKeage K. Bortezomib: a review of its use in patients with multiple myeloma.. Drugs 2009;69(7):859-88.
    doi: 10.2165/00003495-200969070-00006pubmed: 19441872google scholar: lookup
  5. Mateos MV. Role of bortezomib for the treatment of previously untreated multiple myeloma.. Expert Rev Hematol 2008 Oct;1(1):17-28.
    doi: 10.1586/17474086.1.1.17pubmed: 21083004google scholar: lookup
  6. Schneider M, Ackermann K, Stuart M, Wex C, Protzer U, Schätzl HM, Gilch S. Severe acute respiratory syndrome coronavirus replication is severely impaired by MG132 due to proteasome-independent inhibition of M-calpain.. J Virol 2012 Sep;86(18):10112-22.
    doi: 10.1128/JVI.01001-12pmc: PMC3446591pubmed: 22787216google scholar: lookup
  7. Khor R, McElroy LJ, Whittaker GR. The ubiquitin-vacuolar protein sorting system is selectively required during entry of influenza virus into host cells.. Traffic 2003 Dec;4(12):857-68.
    pubmed: 14617349doi: 10.1046/j.1398-9219.2003.0140.xgoogle scholar: lookup
  8. Widjaja I, de Vries E, Tscherne DM, García-Sastre A, Rottier PJ, de Haan CA. Inhibition of the ubiquitin-proteasome system affects influenza A virus infection at a postfusion step.. J Virol 2010 Sep;84(18):9625-31.
    doi: 10.1128/JVI.01048-10pmc: PMC2937638pubmed: 20631148google scholar: lookup
  9. Delboy MG, Roller DG, Nicola AV. Cellular proteasome activity facilitates herpes simplex virus entry at a postpenetration step.. J Virol 2008 Apr;82(7):3381-90.
    doi: 10.1128/JVI.02296-07pmc: PMC2268500pubmed: 18234803google scholar: lookup
  10. Si X, McManus BM, Zhang J, Yuan J, Cheung C, Esfandiarei M, Suarez A, Morgan A, Luo H. Pyrrolidine dithiocarbamate reduces coxsackievirus B3 replication through inhibition of the ubiquitin-proteasome pathway.. J Virol 2005 Jul;79(13):8014-23.
    pmc: PMC1143712pubmed: 15956547doi: 10.1128/JVI.79.13.8014-8023.2005google scholar: lookup
  11. Raaben M, Posthuma CC, Verheije MH, te Lintelo EG, Kikkert M, Drijfhout JW, Snijder EJ, Rottier PJ, de Haan CA. The ubiquitin-proteasome system plays an important role during various stages of the coronavirus infection cycle.. J Virol 2010 Aug;84(15):7869-79.
    doi: 10.1128/JVI.00485-10pmc: PMC2897594pubmed: 20484504google scholar: lookup
  12. Horan KA, Hansen K, Jakobsen MR, Holm CK, Søby S, Unterholzner L, Thompson M, West JA, Iversen MB, Rasmussen SB, Ellermann-Eriksen S, Kurt-Jones E, Landolfo S, Damania B, Melchjorsen J, Bowie AG, Fitzgerald KA, Paludan SR. Proteasomal degradation of herpes simplex virus capsids in macrophages releases DNA to the cytosol for recognition by DNA sensors.. J Immunol 2013 Mar 1;190(5):2311-9.
    doi: 10.4049/jimmunol.1202749pmc: PMC3578088pubmed: 23345332google scholar: lookup
  13. Schubert U, Ott DE, Chertova EN, Welker R, Tessmer U, Princiotta MF, Bennink JR, Krausslich HG, Yewdell JW. Proteasome inhibition interferes with gag polyprotein processing, release, and maturation of HIV-1 and HIV-2.. Proc Natl Acad Sci U S A 2000 Nov 21;97(24):13057-62.
    pmc: PMC27177pubmed: 11087859doi: 10.1073/pnas.97.24.13057google scholar: lookup
  14. Aguilar PV, Greene IP, Coffey LL, Medina G, Moncayo AC, Anishchenko M, Ludwig GV, Turell MJ, O'Guinn ML, Lee J, Tesh RB, Watts DM, Russell KL, Hice C, Yanoviak S, Morrison AC, Klein TA, Dohm DJ, Guzman H, Travassos da Rosa AP, Guevara C, Kochel T, Olson J, Cabezas C, Weaver SC. Endemic Venezuelan equine encephalitis in northern Peru.. Emerg Infect Dis 2004 May;10(5):880-8.
    pmc: PMC3323213pubmed: 15200823doi: 10.3201/eid1005.030634google scholar: lookup
  15. Foy NJ, Akhrymuk M, Akhrymuk I, Atasheva S, Bopda-Waffo A, Frolov I, Frolova EI. Hypervariable domains of nsP3 proteins of New World and Old World alphaviruses mediate formation of distinct, virus-specific protein complexes.. J Virol 2013 Feb;87(4):1997-2010.
    doi: 10.1128/JVI.02853-12pmc: PMC3571466pubmed: 23221551google scholar: lookup
  16. Kim DY, Atasheva S, Frolova EI, Frolov I. Venezuelan equine encephalitis virus nsP2 protein regulates packaging of the viral genome into infectious virions.. J Virol 2013 Apr;87(8):4202-13.
    doi: 10.1128/JVI.03142-12pmc: PMC3624340pubmed: 23365438google scholar: lookup
  17. Lamb K, Lokesh GL, Sherman M, Watowich S. Structure of a Venezuelan equine encephalitis virus assembly intermediate isolated from infected cells.. Virology 2010 Oct 25;406(2):261-9.
    doi: 10.1016/j.virol.2010.07.009pmc: PMC2939143pubmed: 20701942google scholar: lookup
  18. Steele KE, Twenhafel NA. REVIEW PAPER: pathology of animal models of alphavirus encephalitis.. Vet Pathol 2010 Sep;47(5):790-805.
    doi: 10.1177/0300985810372508pubmed: 20551475google scholar: lookup
  19. Bhomia M, Sharma A, Gayen M, Gupta P, Maheshwari RK. Artificial microRNAs can effectively inhibit replication of Venezuelan equine encephalitis virus.. Antiviral Res 2013 Nov;100(2):429-34.
    doi: 10.1016/j.antiviral.2013.08.010pmc: PMC7113778pubmed: 23988697google scholar: lookup
  20. Tretyakova I, Lukashevich IS, Glass P, Wang E, Weaver S, Pushko P. Novel vaccine against Venezuelan equine encephalitis combines advantages of DNA immunization and a live attenuated vaccine.. Vaccine 2013 Feb 4;31(7):1019-25.
    doi: 10.1016/j.vaccine.2012.12.050pmc: PMC3556218pubmed: 23287629google scholar: lookup
  21. Zacks MA, Paessler S. Encephalitic alphaviruses.. Vet Microbiol 2010 Jan 27;140(3-4):281-6.
    doi: 10.1016/j.vetmic.2009.08.023pmc: PMC2814892pubmed: 19775836google scholar: lookup
  22. Spurgers KB, Hurt CR, Cohen JW, Eccelston LT, Lind CM, Lingappa VR, Glass PJ. Validation of a cell-based ELISA as a screening tool identifying anti-alphavirus small-molecule inhibitors.. J Virol Methods 2013 Oct;193(1):226-31.
    doi: 10.1016/j.jviromet.2013.06.007pubmed: 23764417google scholar: lookup
  23. Barber TL, Walton TE, Lewis KJ. Efficacy of trivalent inactivated encephalomyelitis virus vaccine in horses.. Am J Vet Res 1978 Apr;39(4):621-5.
    pubmed: 646197
  24. Garmashova N, Gorchakov R, Volkova E, Paessler S, Frolova E, Frolov I. The Old World and New World alphaviruses use different virus-specific proteins for induction of transcriptional shutoff.. J Virol 2007 Mar;81(5):2472-84.
    pmc: PMC1865960pubmed: 17108023doi: 10.1128/JVI.02073-06google scholar: lookup
  25. Weaver SC, Ferro C, Barrera R, Boshell J, Navarro JC. Venezuelan equine encephalitis.. Annu Rev Entomol 2004;49:141-74.
    pubmed: 14651460doi: 10.1146/annurev.ento.49.061802.123422google scholar: lookup
  26. Jose J, Snyder JE, Kuhn RJ. A structural and functional perspective of alphavirus replication and assembly.. Future Microbiol 2009 Sep;4(7):837-56.
    doi: 10.2217/fmb.09.59pmc: PMC2762864pubmed: 19722838google scholar: lookup
  27. Weaver SC, Barrett AD. Transmission cycles, host range, evolution and emergence of arboviral disease.. Nat Rev Microbiol 2004 Oct;2(10):789-801.
    pmc: PMC7097645pubmed: 15378043doi: 10.1038/nrmicro1006google scholar: lookup
  28. Amaya M, Voss K, Sampey G, Senina S, de la Fuente C, Mueller C, Calvert V, Kehn-Hall K, Carpenter C, Kashanchi F, Bailey C, Mogelsvang S, Petricoin E, Narayanan A. The role of IKKβ in Venezuelan equine encephalitis virus infection.. PLoS One 2014;9(2):e86745.
    doi: 10.1371/journal.pone.0086745pmc: PMC3929299pubmed: 24586253google scholar: lookup
  29. Atasheva S, Fish A, Fornerod M, Frolova EI. Venezuelan equine Encephalitis virus capsid protein forms a tetrameric complex with CRM1 and importin alpha/beta that obstructs nuclear pore complex function.. J Virol 2010 May;84(9):4158-71.
    doi: 10.1128/JVI.02554-09pmc: PMC2863722pubmed: 20147401google scholar: lookup
  30. Atasheva S, Krendelchtchikova V, Liopo A, Frolova E, Frolov I. Interplay of acute and persistent infections caused by Venezuelan equine encephalitis virus encoding mutated capsid protein.. J Virol 2010 Oct;84(19):10004-15.
    doi: 10.1128/JVI.01151-10pmc: PMC2937817pubmed: 20668087google scholar: lookup
  31. Garmashova N, Atasheva S, Kang W, Weaver SC, Frolova E, Frolov I. Analysis of Venezuelan equine encephalitis virus capsid protein function in the inhibition of cellular transcription.. J Virol 2007 Dec;81(24):13552-65.
    pmc: PMC2168819pubmed: 17913819doi: 10.1128/JVI.01576-07google scholar: lookup
  32. Kinney RM, Johnson BJ, Welch JB, Tsuchiya KR, Trent DW. The full-length nucleotide sequences of the virulent Trinidad donkey strain of Venezuelan equine encephalitis virus and its attenuated vaccine derivative, strain TC-83.. Virology 1989 May;170(1):19-30.
    pubmed: 2524126doi: 10.1016/0042-6822(89)90347-4google scholar: lookup
  33. Narayanan A, Kehn-Hall K, Senina S, Lundberg L, Van Duyne R, Guendel I, Das R, Baer A, Bethel L, Turell M, Hartman AL, Das B, Bailey C, Kashanchi F. Curcumin inhibits Rift Valley fever virus replication in human cells.. J Biol Chem 2012 Sep 28;287(40):33198-214.
    pmc: PMC3460426pubmed: 22847000doi: 10.1074/jbc.M112.356535google scholar: lookup
  34. Kehn-Hall K, Narayanan A, Lundberg L, Sampey G, Pinkham C, Guendel I, Van Duyne R, Senina S, Schultz KL, Stavale E, Aman MJ, Bailey C, Kashanchi F. Modulation of GSK-3β activity in Venezuelan equine encephalitis virus infection.. PLoS One 2012;7(4):e34761.
    doi: 10.1371/journal.pone.0034761pmc: PMC3319612pubmed: 22496857google scholar: lookup
  35. Julander JG, Skirpstunas R, Siddharthan V, Shafer K, Hoopes JD, Smee DF, Morrey JD. C3H/HeN mouse model for the evaluation of antiviral agents for the treatment of Venezuelan equine encephalitis virus infection.. Antiviral Res 2008 Jun;78(3):230-41.
    doi: 10.1016/j.antiviral.2008.01.007pmc: PMC2396595pubmed: 18313150google scholar: lookup
  36. Guo N, Peng Z. MG132, a proteasome inhibitor, induces apoptosis in tumor cells.. Asia Pac J Clin Oncol 2013 Mar;9(1):6-11.
    doi: 10.1111/j.1743-7563.2012.01535.xpubmed: 22897979google scholar: lookup
  37. Taylor RT, Best SM. Assessing ubiquitination of viral proteins: Lessons from flavivirus NS5.. Methods 2011 Oct;55(2):166-71.
    doi: 10.1016/j.ymeth.2011.08.003pmc: PMC3208789pubmed: 21855635google scholar: lookup
  38. Pisano MB, Oria G, Beskow G, Aguilar J, Konigheim B, Cacace ML, Aguirre L, Stein M, Contigiani MS. Venezuelan equine encephalitis viruses (VEEV) in Argentina: serological evidence of human infection.. PLoS Negl Trop Dis 2013;7(12):e2551.
    doi: 10.1371/journal.pntd.0002551pmc: PMC3861189pubmed: 24349588google scholar: lookup
  39. Randow F, Lehner PJ. Viral avoidance and exploitation of the ubiquitin system.. Nat Cell Biol 2009 May;11(5):527-34.
    doi: 10.1038/ncb0509-527pubmed: 19404332google scholar: lookup
  40. Kisselev AF, Goldberg AL. Proteasome inhibitors: from research tools to drug candidates.. Chem Biol 2001 Aug;8(8):739-58.
    pubmed: 11514224doi: 10.1016/s1074-5521(01)00056-4google scholar: lookup
  41. Lee DH, Goldberg AL. Proteasome inhibitors: valuable new tools for cell biologists.. Trends Cell Biol 1998 Oct;8(10):397-403.
    pubmed: 9789328doi: 10.1016/s0962-8924(98)01346-4google scholar: lookup
  42. Ma XZ, Bartczak A, Zhang J, Khattar R, Chen L, Liu MF, Edwards A, Levy G, McGilvray ID. Proteasome inhibition in vivo promotes survival in a lethal murine model of severe acute respiratory syndrome.. J Virol 2010 Dec;84(23):12419-28.
    doi: 10.1128/JVI.01219-10pmc: PMC2976395pubmed: 20861244google scholar: lookup
  43. Wang YE, Park A, Lake M, Pentecost M, Torres B, Yun TE, Wolf MC, Holbrook MR, Freiberg AN, Lee B. Ubiquitin-regulated nuclear-cytoplasmic trafficking of the Nipah virus matrix protein is important for viral budding.. PLoS Pathog 2010 Nov 11;6(11):e1001186.
    doi: 10.1371/journal.ppat.1001186pmc: PMC2978725pubmed: 21085610google scholar: lookup

Citations

This article has been cited 18 times.
  1. Yin P, Jian X, Liu Y, Liu Y, Lv L, Cui H, Zhang L. Elucidating cellular interactome of chikungunya virus identifies host dependency factors.. Virol Sin 2023 Aug;38(4):497-507.
    doi: 10.1016/j.virs.2023.05.007pubmed: 37182691google scholar: lookup
  2. Boghdeh NA, McGraw B, Barrera MD, Anderson C, Baha H, Risner KH, Ogungbe IV, Alem F, Narayanan A. Inhibitors of the Ubiquitin-Mediated Signaling Pathway Exhibit Broad-Spectrum Antiviral Activities against New World Alphaviruses.. Viruses 2023 Feb 28;15(3).
    doi: 10.3390/v15030655pubmed: 36992362google scholar: lookup
  3. Boghdeh NA, Risner KH, Barrera MD, Britt CM, Schaffer DK, Alem F, Brown JA, Wikswo JP, Narayanan A. Application of a Human Blood Brain Barrier Organ-on-a-Chip Model to Evaluate Small Molecule Effectiveness against Venezuelan Equine Encephalitis Virus.. Viruses 2022 Dec 15;14(12).
    doi: 10.3390/v14122799pubmed: 36560802google scholar: lookup
  4. Andreolla AP, Borges AA, Bordignon J, Duarte Dos Santos CN. Mayaro Virus: The State-of-the-Art for Antiviral Drug Development.. Viruses 2022 Aug 16;14(8).
    doi: 10.3390/v14081787pubmed: 36016409google scholar: lookup
  5. Yang J, Liu X. Immunotherapy for Refractory Autoimmune Encephalitis.. Front Immunol 2021;12:790962.
    doi: 10.3389/fimmu.2021.790962pubmed: 34975890google scholar: lookup
  6. Mahajan S, Choudhary S, Kumar P, Tomar S. Antiviral strategies targeting host factors and mechanisms obliging +ssRNA viral pathogens.. Bioorg Med Chem 2021 Sep 15;46:116356.
    doi: 10.1016/j.bmc.2021.116356pubmed: 34416512google scholar: lookup
  7. Gebhart NN, Hardy RW, Sokoloski KJ. Comparative analyses of alphaviral RNA:Protein complexes reveals conserved host-pathogen interactions.. PLoS One 2020;15(8):e0238254.
    doi: 10.1371/journal.pone.0238254pubmed: 32841293google scholar: lookup
  8. Schneider SM, Pritchard SM, Wudiri GA, Trammell CE, Nicola AV. Early Steps in Herpes Simplex Virus Infection Blocked by a Proteasome Inhibitor.. mBio 2019 May 14;10(3).
    doi: 10.1128/mBio.00732-19pubmed: 31088925google scholar: lookup
  9. Llamas-González YY, Campos D, Pascale JM, Arbiza J, González-Santamaría J. A Functional Ubiquitin-Proteasome System is Required for Efficient Replication of New World Mayaro and Una Alphaviruses.. Viruses 2019 Apr 23;11(4).
    doi: 10.3390/v11040370pubmed: 31018496google scholar: lookup
  10. Lv BM, Tong XY, Quan Y, Liu MY, Zhang QY, Song YF, Zhang HY. Drug Repurposing for Japanese Encephalitis Virus Infection by Systems Biology Methods.. Molecules 2018 Dec 18;23(12).
    doi: 10.3390/molecules23123346pubmed: 30567313google scholar: lookup
  11. Carey BD, Ammosova T, Pinkham C, Lin X, Zhou W, Liotta LA, Nekhai S, Kehn-Hall K. Protein Phosphatase 1α Interacts with Venezuelan Equine Encephalitis Virus Capsid Protein and Regulates Viral Replication through Modulation of Capsid Phosphorylation.. J Virol 2018 Aug 1;92(15).
    doi: 10.1128/JVI.02068-17pubmed: 29769351google scholar: lookup
  12. LaPointe AT, Gebhart NN, Meller ME, Hardy RW, Sokoloski KJ. Identification and Characterization of Sindbis Virus RNA-Host Protein Interactions.. J Virol 2018 Apr 1;92(7).
    doi: 10.1128/JVI.02171-17pubmed: 29321325google scholar: lookup
  13. Ching KC, F P Ng L, Chai CLL. A compendium of small molecule direct-acting and host-targeting inhibitors as therapies against alphaviruses.. J Antimicrob Chemother 2017 Nov 1;72(11):2973-2989.
    doi: 10.1093/jac/dkx224pubmed: 28981632google scholar: lookup
  14. Lundberg L, Carey B, Kehn-Hall K. Venezuelan Equine Encephalitis Virus Capsid-The Clever Caper.. Viruses 2017 Sep 29;9(10).
    doi: 10.3390/v9100279pubmed: 28961161google scholar: lookup
  15. Wang XY, Yu HZ, Xu JP, Zhang SZ, Yu D, Liu MH, Wang LL. Comparative Subcellular Proteomics Analysis of Susceptible and Near-isogenic Resistant Bombyx mori (Lepidoptera) Larval Midgut Response to BmNPV infection.. Sci Rep 2017 Mar 31;7:45690.
    doi: 10.1038/srep45690pubmed: 28361957google scholar: lookup
  16. Keck F, Brooks-Faulconer T, Lark T, Ravishankar P, Bailey C, Salvador-Morales C, Narayanan A. Altered mitochondrial dynamics as a consequence of Venezuelan Equine encephalitis virus infection.. Virulence 2017 Nov 17;8(8):1849-1866.
    doi: 10.1080/21505594.2016.1276690pubmed: 28075229google scholar: lookup
  17. Amaya M, Brooks-Faulconer T, Lark T, Keck F, Bailey C, Raman V, Narayanan A. Venezuelan equine encephalitis virus non-structural protein 3 (nsP3) interacts with RNA helicases DDX1 and DDX3 in infected cells.. Antiviral Res 2016 Jul;131:49-60.
    doi: 10.1016/j.antiviral.2016.04.008pubmed: 27105836google scholar: lookup
  18. Keck F, Ataey P, Amaya M, Bailey C, Narayanan A. Phosphorylation of Single Stranded RNA Virus Proteins and Potential for Novel Therapeutic Strategies.. Viruses 2015 Oct 12;7(10):5257-73.
    doi: 10.3390/v7102872pubmed: 26473910google scholar: lookup
Subscribe to our newsletter
Join 99,344 horse owners like you who receive our email updates on horse health and nutrition.