Analyze Diet
Virology2008; 377(2); 248-254; doi: 10.1016/j.virol.2008.04.041

Equine arteritis virus is delivered to an acidic compartment of host cells via clathrin-dependent endocytosis.

Abstract: Equine arteritis virus (EAV) is an enveloped, positive-stranded RNA virus belonging to the family Arteriviridae. Infection by EAV requires the release of the viral genome by fusion with the respective target membrane of the host cell. We have investigated the entry pathway of EAV into Baby Hamster Kidney cells (BHK). Infection of cells assessed by the plaque reduction assay was strongly inhibited by substances which interfere with clathrin-dependent endocytosis and by lysosomotropic compounds. Furthermore, infection of BHK cells was suppressed when clathrin-dependent endocytosis was inhibited by expression of antisense RNA of the clathrin-heavy chain before infection. These results strongly suggest that EAV is taken up via clathrin-dependent endocytosis and is delivered to acidic endosomal compartments.
Publication Date: 2008-06-24 PubMed ID: 18570963PubMed Central: PMC7103380DOI: 10.1016/j.virol.2008.04.041Google 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.
  • 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.

The research indicates that the Equine arteritis virus (EAV) infects host cells through a process known as clathrin-dependent endocytosis, and is then delivered to the acidic compartments of those cells.

Overall Approach to the Research

  • The researchers studied how the Equine arteritis virus (EAV), a type of RNA virus, enters and infects Baby Hamster Kidney cells (BHK).
  • They specifically looked at whether the process of clathrin-dependent endocytosis, a specific procedure by which cells absorb materials from their surroundings, played a role in the virus’s infection process.

Experimentation and Findings

  • During the investigations, the researchers used substances that interfere with clathrin-dependent endocytosis and lysosomotropic compounds to examine how they affected the infection process of the EAV.
  • The infection of the BHK cells was found to be strongly inhibited—meaning the virus was less effective—when these substances were used.
  • In addition, when clathrin-dependent endocytosis was suppressed in the BHK cells through the expression of antisense RNA of the clathrin-heavy chain, the infection rate of EAV was also reduced.

Conclusions

  • Based on these findings, the researchers concluded that the EAV virus enters host cells through clathrin-dependent endocytosis.
  • Moreover, once the virus is inside the host cell, it’s delivered to acidic compartments within the cell, a step essential for the virus reproduction and further infection.

Implications

  • This study provides valuable insights into the mechanisms that EAV uses to infect cells, contributing to the broader understanding of how RNA viruses operate.
  • The findings can aid in the development of new antiviral strategies that target these specific processes to inhibit viral infection, particular focusing on blocking the clathrin-dependent endocytosis pathway.

Cite This Article

APA
Nitschke M, Korte T, Tielesch C, Ter-Avetisyan G, Tünnemann G, Cardoso MC, Veit M, Herrmann A. (2008). Equine arteritis virus is delivered to an acidic compartment of host cells via clathrin-dependent endocytosis. Virology, 377(2), 248-254. https://doi.org/10.1016/j.virol.2008.04.041

Publication

ISSN: 0042-6822
NlmUniqueID: 0110674
Country: United States
Language: English
Volume: 377
Issue: 2
Pages: 248-254

Researcher Affiliations

Nitschke, Matthias
  • Department of Biology/Biophysics, Humboldt University Berlin, Invalidenstr. 42, 10115 Berlin, Germany.
Korte, Thomas
    Tielesch, Claudia
      Ter-Avetisyan, Gohar
        Tünnemann, Gisela
          Cardoso, M Cristina
            Veit, Michael
              Herrmann, Andreas

                MeSH Terms

                • Animals
                • Arterivirus Infections / metabolism
                • Cell Line
                • Clathrin / metabolism
                • Cricetinae
                • Endocytosis / drug effects
                • Endocytosis / physiology
                • Endosomes / metabolism
                • Endosomes / virology
                • Equartevirus / genetics
                • Equartevirus / metabolism
                • Equartevirus / physiology

                References

                This article includes 35 references
                1. Brindley M.A., Maury W.. Endocytosis and a low-pH step are required for productive entry of equine infectious anemia virus.. J. Virol. 2005;79(23):14482–14488.
                  pmc: PMC1287591pubmed: 16282447
                2. Brindley M.A., Hughes L., Ruiz A., McCray P.B., Jr., Sanchez A., Sanders D.A., Maury W.. Ebola virus glycoprotein 1: identification of residues important for binding and postbinding events.. J. Virol. 2007;81(14):7702–7709.
                  pmc: PMC1933332pubmed: 17475648
                3. Chandran K., Sullivan N.J., Felbor U., Whelan S.P., Cunningham J.M.. Endosomal proteolysis of the Ebola virus glycoprotein is necessary for infection.. Science 2005;308(5728):1643–1645.
                  pmc: PMC4797943pubmed: 15831716
                4. Choi K.S., Aizaki H., Lai M.M.. Murine coronavirus requires lipid rafts for virus entry and cell–cell fusion but not for virus release.. J. Virol. 2005;79(15):9862–9871.
                  pmc: PMC1181594pubmed: 16014947
                5. de Vries A.A., Chirnside E.D., Horzinek M.C., Rottier P.J.. Structural proteins of equine arteritis virus.. J. Virol. 1992;66(11)):6294–6303.
                  pmc: PMC240121pubmed: 1328669
                6. Deregt D., de Vries A.A., Raamsman M.J., Elmgren L.D., Rottier P.J.. Monoclonal antibodies to equine arteritis virus proteins identify the GL protein as a target for virus neutralization.. J. Gen. Virol. 1994;75(Pt 9):2439–2444.
                  pubmed: 8077945
                7. Doll E.R., Bryans J.T., Crowe M.E., McCollum W.H.. Isolation of a filterable agent causing arteritis of horses and abortion by mares; its differentiation from the equine abortion, (influenza) virus.. Cornell Vet. 1957;47(1):3–41.
                  pubmed: 13397177
                8. Drose S., Altendorf K.. Bafilomycins and concanamycins as inhibitors of V-ATPases and P-ATPases.. J. Exp. Biol. 1997;200(Pt 1):1–8.
                  pubmed: 9023991
                9. Earp L.J., Delos S.E., Park H.E., White J.M.. The many mechanisms of viral membrane fusion proteins.. Curr. Top. Microbiol. Immunol. 2005;285:25–66.
                  pmc: PMC7122167pubmed: 15609500
                10. Eifart P., Ludwig K., Böttcher C., de Haan C.A.M., Rottier P.J.M., Korte T., Herrmann A.. The role of endocytosis and low pH in cell entry of the murine hepatitis virus MHV-A59.. J. Virol. 2007;81:10758–10768.
                  pmc: PMC2045462pubmed: 17626088
                11. Guyader M., Kiyokawa E., Abrami L., Turelli P., Trono D.. Role for human immunodeficiency virus type 1 membrane cholesterol in viral internalization.. J. Virol. 2002;76(20):10356–10364.
                  pmc: PMC136590pubmed: 12239312
                12. Iversen T.G., Skretting G., Llorente A., Nicoziani P., van Deurs B., Sandvig K.. Endosome to Golgi transport of ricin is independent of clathrin and of the Rab9- and Rab11-GTPases.. Mol. Biol. Cell. 2001;12(7):2099–2107.
                  pmc: PMC55659pubmed: 11452006
                13. Jin S., Zhang B., Weisz O.A., Montelaro R.C.. Receptor-mediated entry by equine infectious anemia virus utilizes a pH-dependent endocytic pathway.. J. Virol. 2005;79(23):14489–14497.
                  pmc: PMC1287590pubmed: 16282448
                14. Kooi C., Cervin M., Anderson R.. Differentiation of acid-pH dependent and -nondependent entry pathways for mouse hepatitis virus.. Virology 1991;180(1):108–109.
                  pmc: PMC7131382pubmed: 1845820
                15. Korte T., Ludwig K., Booy F.P., Blumenthal R., Herrmann A.. Conformational intermediates and fusion activity of influenza virus hemagglutinin.. J. Virol. 1999;73(6):4567–4574.
                  pmc: PMC112497pubmed: 10233915
                16. Kreutz L.C., Ackermann M.R.. Porcine reproductive and respiratory syndrome virus enters cells through a low pH-dependent endocytic pathway.. Virus Res. 1996;42(1–2):137–147.
                  pubmed: 8806181
                17. Lamb R.A., Kolakofsky D.. Fields Virology. 4th Edition. 2001. Paramyxoviridae: the viruses and their replication.. .
                18. Marsh M., Helenius A.. Virus entry: open sesame.. Cell 2006;124(4):729–740.
                  pmc: PMC7112260pubmed: 16497584
                19. Mothes W., Boerger A.L., Narayan S., Cunningham J.M., Young J.A.. Retroviral entry mediated by receptor priming and low pH triggering of an envelope glycoprotein.. Cell 2000;103(4):679–689.
                  pubmed: 11106737
                20. Nash T.C., Buchmeier M.J.. Entry of mouse hepatitis virus into cells by endosomal and nonendosomal pathways.. Virology 1997;233(1):1–8.
                  pubmed: 9201212
                21. Nauwynck H.J., Duan X., Favoreel H.W., Van Oostveldt P., Pensaert M.B.. Entry of porcine reproductive and respiratory syndrome virus into porcine alveolar macrophages via receptor-mediated endocytosis.. J. Gen. Virol. 1999;80(Pt 2):297–305.
                  pubmed: 10073688
                22. Ohkuma S., Poole B.. Fluorescence probe measurement of the intralysosomal pH in living cells and the perturbation of pH by various agents.. Proc. Natl. Acad. Sci. U. S. A. 1978;75(7):3327–3331.
                  pmc: PMC392768pubmed: 28524
                23. Perez L., Carrasco L.. Involvement of the vacuolar H(+)-ATPase in animal virus entry.. J. Gen. Virol. 1994;75(Pt 10):2595–2606.
                  pubmed: 7931146
                24. Puri A., Booy F.P., Doms R.W., White J.M., Blumenthal R.. Conformational changes and fusion activity of influenza virus hemagglutinin of the H2 and H3 subtypes: effects of acid pretreatment.. J. Virol. 1990;64(8):3824–3832.
                  pmc: PMC249678pubmed: 2196382
                25. Qiu Z., Hingley S.T., Simmons G., Yu C., Das Sarma J., Bates P., Weiss S.R.. Endosomal proteolysis by cathepsins is necessary for murine coronavirus mouse hepatitis virus type 2 spike-mediated entry.. J. Virol. 2006;80(12):5768–5776.
                  pmc: PMC1472567pubmed: 16731916
                26. Rodal S.K., Skretting G., Garred O., Vilhardt F., van Deurs B., Sandvig K.. Extraction of cholesterol with methyl-beta-cyclodextrin perturbs formation of clathrin-coated endocytic vesicles.. Mol. Biol. Cell. 1999;10(4):961–974.
                  pmc: PMC25220pubmed: 10198050
                27. Simmons G., Gosalia D.N., Rennekamp A.J., Reeves J.D., Diamond S.L., Bates P.. Inhibitors of cathepsin L prevent severe acute respiratory syndrome coronavirus entry.. Proc. Natl. Acad. Sci. U. S. A. 2005;102(33):11876–11881.
                  pmc: PMC1188015pubmed: 16081529
                28. Snijder E.J., Meulenberg J.J.. The molecular biology of arteriviruses.. J. Gen. Virol. 1998;79,(Pt 5):961–979.
                  pubmed: 9603311
                29. Subtil A., Gaidarov I., Kobylarz K., Lampson M.A., Keen J.H., McGraw T.E.. Acute cholesterol depletion inhibits clathrin-coated pit budding.. Proc. Natl. Acad. Sci. U. S. A. 1999;96(12):6775–6780.
                  pmc: PMC21991pubmed: 10359788
                30. van Dinten L.C., den Boon J.A., Wassenaar A.L., Spaan W.J., Snijder E.J.. An infectious arterivirus cDNA clone: identification of a replicase point mutation that abolishes discontinuous mRNA transcription.. Proc. Natl. Acad. Sci. U. S. A. 1997;94(3):991–996.
                  pmc: PMC19627pubmed: 9023370
                31. Wada R., Fukunaga Y., Kondo T., Kanemaru T.. Ultrastructure and immuno-cytochemistry of BHK-21 cells infected with a modified Bucyrus strain of equine arteritis virus.. Arch. Virol. 1995;140(7):1173–1180.
                  pmc: PMC7086595pubmed: 7646351
                32. Wang L.H., Rothberg K.G., Anderson R.G.. Mis-assembly of clathrin lattices on endosomes reveals a regulatory switch for coated pit formation.. J. Cell Biol. 1993;123(5):1107–1117.
                  pmc: PMC2119875pubmed: 8245121
                33. Wieringa R., De Vries A.A., Post S.M., Rottier P.J.. Intra- and intermolecular disulfide bonds of the GP2b glycoprotein of equine arteritis virus: relevance for virus assembly and infectivity.. J. Virol. 2003;77(24):12996–13004.
                  pmc: PMC296049pubmed: 14645556
                34. Wieringa R., de Vries A.A., van der Meulen J., Godeke G.J., Onderwater J.J., van Tol H., Koerten H.K., Mommaas A.M., Snijder E.J., Rottier P.J.. Structural protein requirements in equine arteritis virus assembl.. J. Virol. 2004;78(23):13019–13027.
                  pmc: PMC524988pubmed: 15542653
                35. Yumoto R., Nishikawa H., Okamoto M., Katayama H., Nagai J., Takano M.. Clathrin-mediated endocytosis of FITC-albumin in alveolar type II epithelial cell line RLE-6TN.. Am. J. Physiol. Lung Cell Mol. Physiol. 2006;290(5):L946–L955.
                  pubmed: 16361359

                Citations

                This article has been cited 16 times.
                1. Kublicka A, Lorek D, Mikołajczyk-Martinez A, Chodaczek G, Chwirot A, Bażanów B, Matczuk AK. Imaging flow cytometry reveals the mechanism of equine arteritis virus entry and internalization. Sci Rep 2025 Jan 25;15(1):3246.
                  doi: 10.1038/s41598-025-87080-xpubmed: 39863680google scholar: lookup
                2. Anderson C, Baha H, Boghdeh N, Barrera M, Alem F, Narayanan A. Interactions of Equine Viruses with the Host Kinase Machinery and Implications for One Health and Human Disease. Viruses 2023 May 13;15(5).
                  doi: 10.3390/v15051163pubmed: 37243249google scholar: lookup
                3. Veit M, Gadalla MR, Zhang M. Using Alphafold2 to Predict the Structure of the Gp5/M Dimer of Porcine Respiratory and Reproductive Syndrome Virus. Int J Mol Sci 2022 Oct 30;23(21).
                  doi: 10.3390/ijms232113209pubmed: 36361998google scholar: lookup
                4. Zhang M, Han X, Osterrieder K, Veit M. Palmitoylation of the envelope membrane proteins GP5 and M of porcine reproductive and respiratory syndrome virus is essential for virus growth. PLoS Pathog 2021 Apr;17(4):e1009554.
                  doi: 10.1371/journal.ppat.1009554pubmed: 33891658google scholar: lookup
                5. Jeon JH, Lee C. Cellular cholesterol is required for porcine nidovirus infection. Arch Virol 2017 Dec;162(12):3753-3767.
                  doi: 10.1007/s00705-017-3545-4pubmed: 28884395google scholar: lookup
                6. Sarkar S, Chelvarajan L, Go YY, Cook F, Artiushin S, Mondal S, Anderson K, Eberth J, Timoney PJ, Kalbfleisch TS, Bailey E, Balasuriya UB. Equine Arteritis Virus Uses Equine CXCL16 as an Entry Receptor. J Virol 2016 Jan 13;90(7):3366-84.
                  doi: 10.1128/JVI.02455-15pubmed: 26764004google scholar: lookup
                7. Buchmann JP, Holmes EC. Cell Walls and the Convergent Evolution of the Viral Envelope. Microbiol Mol Biol Rev 2015 Dec;79(4):403-18.
                  doi: 10.1128/MMBR.00017-15pubmed: 26378223google scholar: lookup
                8. Caì Y, Postnikova EN, Bernbaum JG, Yú SQ, Mazur S, Deiuliis NM, Radoshitzky SR, Lackemeyer MG, McCluskey A, Robinson PJ, Haucke V, Wahl-Jensen V, Bailey AL, Lauck M, Friedrich TC, O'Connor DH, Goldberg TL, Jahrling PB, Kuhn JH. Simian hemorrhagic fever virus cell entry is dependent on CD163 and uses a clathrin-mediated endocytosis-like pathway. J Virol 2015 Jan;89(1):844-56.
                  doi: 10.1128/JVI.02697-14pubmed: 25355889google scholar: lookup
                9. Veit M, Matczuk AK, Sinhadri BC, Krause E, Thaa B. Membrane proteins of arterivirus particles: structure, topology, processing and function. Virus Res 2014 Dec 19;194:16-36.
                10. Méndez E, Muñoz-Yañez C, Sánchez-San Martín C, Aguirre-Crespo G, Baños-Lara Mdel R, Gutierrez M, Espinosa R, Acevedo Y, Arias CF, López S. Characterization of human astrovirus cell entry. J Virol 2014 Mar;88(5):2452-60.
                  doi: 10.1128/JVI.02908-13pubmed: 24335315google scholar: lookup
                11. Matczuk AK, Kunec D, Veit M. Co-translational processing of glycoprotein 3 from equine arteritis virus: N-glycosylation adjacent to the signal peptide prevents cleavage. J Biol Chem 2013 Dec 6;288(49):35396-405.
                  doi: 10.1074/jbc.M113.505420pubmed: 24142700google scholar: lookup
                12. Balasuriya UB, Go YY, MacLachlan NJ. Equine arteritis virus. Vet Microbiol 2013 Nov 29;167(1-2):93-122.
                  doi: 10.1016/j.vetmic.2013.06.015pubmed: 23891306google scholar: lookup
                13. Kabatek A, Veit M. Folding and oligomerization of the gp2b/gp3/gp4 spike proteins of equine arteritis virus in vitro. Viruses 2012 Mar;4(3):414-23.
                  doi: 10.3390/v4030414pubmed: 22590679google scholar: lookup
                14. Sun Y, Xiao S, Wang D, Luo R, Li B, Chen H, Fang L. Cellular membrane cholesterol is required for porcine reproductive and respiratory syndrome virus entry and release in MARC-145 cells. Sci China Life Sci 2011 Nov;54(11):1011-8.
                  doi: 10.1007/s11427-011-4236-0pubmed: 22173307google scholar: lookup
                15. Go YY, Bailey E, Cook DG, Coleman SJ, Macleod JN, Chen KC, Timoney PJ, Balasuriya UB. Genome-wide association study among four horse breeds identifies a common haplotype associated with in vitro CD3+ T cell susceptibility/resistance to equine arteritis virus infection. J Virol 2011 Dec;85(24):13174-84.
                  doi: 10.1128/JVI.06068-11pubmed: 21994447google scholar: lookup
                16. Ter-Avetisyan G, Tünnemann G, Nowak D, Nitschke M, Herrmann A, Drab M, Cardoso MC. Cell entry of arginine-rich peptides is independent of endocytosis. J Biol Chem 2009 Feb 6;284(6):3370-8.
                  doi: 10.1074/jbc.M805550200pubmed: 19047062google scholar: lookup