This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Desai, P. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Desai, P. J.

 Previous Article  |  Next Article 

Journal of Virology, December 2000, p. 11608-11618, Vol. 74, No. 24
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

A Null Mutation in the UL36 Gene of Herpes Simplex Virus Type 1 Results in Accumulation of Unenveloped DNA-Filled Capsids in the Cytoplasm of Infected Cells

Prashant J. Desai*

Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

Received 18 July 2000/Accepted 18 September 2000

The UL36 open reading frame (ORF) encodes the largest herpes simplex virus type 1 (HSV-1) protein, a 270-kDa polypeptide designated VP1/2, which is also a component of the virion tegument. A null mutation was generated in the UL36 gene to elucidate its role in the virus life cycle. Since the UL36 gene specifies an essential function, complementing cell lines transformed for sequences encoding the UL36 ORF were made. A mutant virus, designated KDelta UL36, that encodes a null mutation in the UL36 gene was isolated and propagated in these cell lines. When noncomplementing cells infected with KDelta UL36 were analyzed, both terminal genomic DNA fragments and DNA-containing capsids (C capsids) were detected; therefore, UL36 is not required for cleavage or packaging of DNA. Sedimentation analysis of lysates from mutant-infected cells revealed the presence of particles that have the physical characteristics of C capsids. In agreement with this, polypeptide profiles of the mutant particles revealed an absence of the major envelope and tegument components. Ultrastructural analysis revealed the presence of numerous unenveloped DNA containing capsids in the cytoplasm of KDelta UL36-infected cells. The UL36 mutant particles were tagged with the VP26-green fluorescent protein marker, and their movement was monitored in living cells. In KDelta UL36-infected cells, extensive particulate fluorescence corresponding to the capsid particles was observed throughout the cytosol. Accumulation of fluorescence at the plasma membrane which indicated maturation and egress of virions was observed in wild-type-infected cells but was absent in KDelta UL36-infected cells. In the absence of UL36 function, DNA-filled capsids are produced; these capsids enter the cytosol after traversing the nuclear envelope and do not mature into enveloped virus. The maturation and egress of the UL36 mutant particles are abrogated, possibly due to a late function of this complex polypeptide, i.e., to target capsids to the correct maturation pathway.


* Mailing address: Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 N. Wolfe St., Baltimore, MD 21205. Phone: (410) 614-1581. Fax: (410) 955-3023. E-mail: pdesai{at}jhmi.edu.


Journal of Virology, December 2000, p. 11608-11618, Vol. 74, No. 24
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.



This article has been cited by other articles:

  • Kim, E. T., Oh, S. E., Lee, Y.-O., Gibson, W., Ahn, J.-H. (2009). Cleavage Specificity of the UL48 Deubiquitinating Protease Activity of Human Cytomegalovirus and the Growth of an Active-Site Mutant Virus in Cultured Cells. J. Virol. 83: 12046-12056 [Abstract] [Full Text]  
  • Pawliczek, T., Crump, C. M. (2009). Herpes Simplex Virus Type 1 Production Requires a Functional ESCRT-III Complex but Is Independent of TSG101 and ALIX Expression. J. Virol. 83: 11254-11264 [Abstract] [Full Text]  
  • Abaitua, F., Souto, R. N., Browne, H., Daikoku, T., O'Hare, P. (2009). Characterization of the herpes simplex virus (HSV)-1 tegument protein VP1-2 during infection with the HSV temperature-sensitive mutant tsB7. J. Gen. Virol. 90: 2353-2363 [Abstract] [Full Text]  
  • Mohl, B. S., Bottcher, S., Granzow, H., Kuhn, J., Klupp, B. G., Mettenleiter, T. C. (2009). Intracellular Localization of the Pseudorabies Virus Large Tegument Protein pUL36. J. Virol. 83: 9641-9651 [Abstract] [Full Text]  
  • Gonzalez, C. M., Wang, L., Damania, B. (2009). Kaposi's Sarcoma-Associated Herpesvirus Encodes a Viral Deubiquitinase. J. Virol. 83: 10224-10233 [Abstract] [Full Text]  
  • Leege, T., Granzow, H., Fuchs, W., Klupp, B. G., Mettenleiter, T. C. (2009). Phenotypic similarities and differences between UL37-deleted pseudorabies virus and herpes simplex virus type 1. J. Gen. Virol. 90: 1560-1568 [Abstract] [Full Text]  
  • Pasdeloup, D., Blondel, D., Isidro, A. L., Rixon, F. J. (2009). Herpesvirus Capsid Association with the Nuclear Pore Complex and Viral DNA Release Involve the Nucleoporin CAN/Nup214 and the Capsid Protein pUL25. J. Virol. 83: 6610-6623 [Abstract] [Full Text]  
  • Stylianou, J., Maringer, K., Cook, R., Bernard, E., Elliott, G. (2009). Virion Incorporation of the Herpes Simplex Virus Type 1 Tegument Protein VP22 Occurs via Glycoprotein E-Specific Recruitment to the Late Secretory Pathway. J. Virol. 83: 5204-5218 [Abstract] [Full Text]  
  • Whitehurst, C. B., Ning, S., Bentz, G. L., Dufour, F., Gershburg, E., Shackelford, J., Langelier, Y., Pagano, J. S. (2009). The Epstein-Barr Virus (EBV) Deubiquitinating Enzyme BPLF1 Reduces EBV Ribonucleotide Reductase Activity. J. Virol. 83: 4345-4353 [Abstract] [Full Text]  
  • Roberts, A. P. E., Abaitua, F., O'Hare, P., McNab, D., Rixon, F. J., Pasdeloup, D. (2009). Differing Roles of Inner Tegument Proteins pUL36 and pUL37 during Entry of Herpes Simplex Virus Type 1. J. Virol. 83: 105-116 [Abstract] [Full Text]  
  • Desai, P., Sexton, G. L., Huang, E., Person, S. (2008). Localization of Herpes Simplex Virus Type 1 UL37 in the Golgi Complex Requires UL36 but Not Capsid Structures. J. Virol. 82: 11354-11361 [Abstract] [Full Text]  
  • Loret, S., Guay, G., Lippe, R. (2008). Comprehensive Characterization of Extracellular Herpes Simplex Virus Type 1 Virions. J. Virol. 82: 8605-8618 [Abstract] [Full Text]  
  • Shanda, S. K., Wilson, D. W. (2008). UL36p Is Required for Efficient Transport of Membrane-Associated Herpes Simplex Virus Type 1 along Microtubules. J. Virol. 82: 7388-7394 [Abstract] [Full Text]  
  • Kalejta, R. F. (2008). Tegument Proteins of Human Cytomegalovirus. Microbiol. Mol. Biol. Rev. 72: 249-265 [Abstract] [Full Text]  
  • Abaitua, F., O'Hare, P. (2008). Identification of a Highly Conserved, Functional Nuclear Localization Signal within the N-Terminal Region of Herpes Simplex Virus Type 1 VP1-2 Tegument Protein. J. Virol. 82: 5234-5244 [Abstract] [Full Text]  
  • Jovasevic, V., Liang, L., Roizman, B. (2008). Proteolytic Cleavage of VP1-2 Is Required for Release of Herpes Simplex Virus 1 DNA into the Nucleus. J. Virol. 82: 3311-3319 [Abstract] [Full Text]  
  • Bottcher, S., Granzow, H., Maresch, C., Mohl, B., Klupp, B. G., Mettenleiter, T. C. (2007). Identification of Functional Domains within the Essential Large Tegument Protein pUL36 of Pseudorabies Virus. J. Virol. 81: 13403-13411 [Abstract] [Full Text]  
  • Coller, K. E., Lee, J. I-H., Ueda, A., Smith, G. A. (2007). The Capsid and Tegument of the Alphaherpesviruses Are Linked by an Interaction between the UL25 and VP1/2 Proteins. J. Virol. 81: 11790-11797 [Abstract] [Full Text]  
  • Fuchs, W., Granzow, H., Klupp, B. G., Karger, A., Michael, K., Maresch, C., Klopfleisch, R., Mettenleiter, T. C. (2007). Relevance of the Interaction between Alphaherpesvirus UL3.5 and UL48 Proteins for Virion Maturation and Neuroinvasion. J. Virol. 81: 9307-9318 [Abstract] [Full Text]  
  • Crump, C. M., Yates, C., Minson, T. (2007). Herpes Simplex Virus Type 1 Cytoplasmic Envelopment Requires Functional Vps4. J. Virol. 81: 7380-7387 [Abstract] [Full Text]  
  • Helferich, D., Veits, J., Mettenleiter, T. C., Fuchs, W. (2007). Identification of transcripts and protein products of the UL31, UL37, UL46, UL47, UL48, UL49 and US4 gene homologues of avian infectious laryngotracheitis virus. J. Gen. Virol. 88: 719-731 [Abstract] [Full Text]  
  • Lee, J. I-H., Luxton, G. W. G., Smith, G. A. (2006). Identification of an Essential Domain in the Herpesvirus VP1/2 Tegument Protein: the Carboxy Terminus Directs Incorporation into Capsid Assemblons. J. Virol. 80: 12086-12094 [Abstract] [Full Text]  
  • Zhu, F. X., Li, X., Zhou, F., Gao, S.-J., Yuan, Y. (2006). Functional Characterization of Kaposi's Sarcoma-Associated Herpesvirus ORF45 by Bacterial Artificial Chromosome-Based Mutagenesis. J. Virol. 80: 12187-12196 [Abstract] [Full Text]  
  • Feederle, R., Neuhierl, B., Baldwin, G., Bannert, H., Hub, B., Mautner, J., Behrends, U., Delecluse, H. J. (2006). Epstein-Barr Virus BNRF1 Protein Allows Efficient Transfer from the Endosomal Compartment to the Nucleus of Primary B Lymphocytes. J. Virol. 80: 9435-9443 [Abstract] [Full Text]  
  • Remillard-Labrosse, G., Guay, G., Lippe, R. (2006). Reconstitution of Herpes Simplex Virus Type 1 Nuclear Capsid Egress In Vitro. J. Virol. 80: 9741-9753 [Abstract] [Full Text]  
  • Bottcher, S., Klupp, B. G., Granzow, H., Fuchs, W., Michael, K., Mettenleiter, T. C. (2006). Identification of a 709-Amino-Acid Internal Nonessential Region within the Essential Conserved Tegument Protein (p)UL36 of Pseudorabies Virus. J. Virol. 80: 9910-9915 [Abstract] [Full Text]  
  • Antinone, S. E., Shubeita, G. T., Coller, K. E., Lee, J. I., Haverlock-Moyns, S., Gross, S. P., Smith, G. A. (2006). The Herpesvirus Capsid Surface Protein, VP26, and the Majority of the Tegument Proteins Are Dispensable for Capsid Transport toward the Nucleus.. J. Virol. 80: 5494-5498 [Abstract] [Full Text]  
  • Wang, J., Loveland, A. N., Kattenhorn, L. M., Ploegh, H. L., Gibson, W. (2006). High-Molecular-Weight Protein (pUL48) of Human Cytomegalovirus Is a Competent Deubiquitinating Protease: Mutant Viruses Altered in Its Active-Site Cysteine or Histidine Are Viable.. J. Virol. 80: 6003-6012 [Abstract] [Full Text]  
  • Lee, G. E., Murray, J. W., Wolkoff, A. W., Wilson, D. W. (2006). Reconstitution of Herpes Simplex Virus Microtubule-Dependent Trafficking In Vitro. J. Virol. 80: 4264-4275 [Abstract] [Full Text]  
  • Luxton, G. W. G., Lee, J. I-H., Haverlock-Moyns, S., Schober, J. M., Smith, G. A. (2006). The Pseudorabies Virus VP1/2 Tegument Protein Is Required for Intracellular Capsid Transport. J. Virol. 80: 201-209 [Abstract] [Full Text]  
  • Hafezi, W., Bernard, E., Cook, R., Elliott, G. (2005). Herpes Simplex Virus Tegument Protein VP22 Contains an Internal VP16 Interaction Domain and a C-Terminal Domain That Are Both Required for VP22 Assembly into the Virus Particle. J. Virol. 79: 13082-13093 [Abstract] [Full Text]  
  • Vittone, V., Diefenbach, E., Triffett, D., Douglas, M. W., Cunningham, A. L., Diefenbach, R. J. (2005). Determination of Interactions between Tegument Proteins of Herpes Simplex Virus Type 1. J. Virol. 79: 9566-9571 [Abstract] [Full Text]  
  • Tischer, B. K., Schumacher, D., Chabanne-Vautherot, D., Zelnik, V., Vautherot, J.-F., Osterrieder, N. (2005). High-Level Expression of Marek's Disease Virus Glycoprotein C Is Detrimental to Virus Growth In Vitro. J. Virol. 79: 5889-5899 [Abstract] [Full Text]  
  • Zhu, F. X., Chong, J. M., Wu, L., Yuan, Y. (2005). Virion Proteins of Kaposi's Sarcoma-Associated Herpesvirus. J. Virol. 79: 800-811 [Abstract] [Full Text]  
  • Thurlow, J. K., Rixon, F. J., Murphy, M., Targett-Adams, P., Hughes, M., Preston, V. G. (2005). The Herpes Simplex Virus Type 1 DNA Packaging Protein UL17 Is a Virion Protein That Is Present in Both the Capsid and the Tegument Compartments. J. Virol. 79: 150-158 [Abstract] [Full Text]  
  • Moorman, N. J., Lin, C. Y., Speck, S. H. (2004). Identification of Candidate Gammaherpesvirus 68 Genes Required for Virus Replication by Signature-Tagged Transposon Mutagenesis. J. Virol. 78: 10282-10290 [Abstract] [Full Text]  
  • Klopfleisch, R., Teifke, J. P., Fuchs, W., Kopp, M., Klupp, B. G., Mettenleiter, T. C. (2004). Influence of Tegument Proteins of Pseudorabies Virus on Neuroinvasion and Transneuronal Spread in the Nervous System of Adult Mice after Intranasal Inoculation. J. Virol. 78: 2956-2966 [Abstract] [Full Text]  
  • Bjerke, S. L., Cowan, J. M., Kerr, J. K., Reynolds, A. E., Baines, J. D., Roller, R. J. (2003). Effects of Charged Cluster Mutations on the Function of Herpes Simplex Virus Type 1 UL34 Protein. J. Virol. 77: 7601-7610 [Abstract] [Full Text]  
  • Lyman, M. G., Demmin, G. L., Banfield, B. W. (2002). The Attenuated Pseudorabies Virus Strain Bartha Fails To Package the Tegument Proteins Us3 and VP22. J. Virol. 77: 1403-1414 [Abstract] [Full Text]  
  • Kopp, M., Klupp, B. G., Granzow, H., Fuchs, W., Mettenleiter, T. C. (2002). Identification and Characterization of the Pseudorabies Virus Tegument Proteins UL46 and UL47: Role for UL47 in Virion Morphogenesis in the Cytoplasm. J. Virol. 76: 8820-8833 [Abstract] [Full Text]  
  • Fuchs, W., Klupp, B. G., Granzow, H., Hengartner, C., Brack, A., Mundt, A., Enquist, L. W., Mettenleiter, T. C. (2002). Physical Interaction between Envelope Glycoproteins E and M of Pseudorabies Virus and the Major Tegument Protein UL49. J. Virol. 76: 8208-8217 [Abstract] [Full Text]  
  • Fuchs, W., Granzow, H., Klupp, B. G., Kopp, M., Mettenleiter, T. C. (2002). The UL48 Tegument Protein of Pseudorabies Virus Is Critical for Intracytoplasmic Assembly of Infectious Virions. J. Virol. 76: 6729-6742 [Abstract] [Full Text]  
  • Ogawa-Goto, K., Irie, S., Omori, A., Miura, Y., Katano, H., Hasegawa, H., Kurata, T., Sata, T., Arao, Y. (2002). An Endoplasmic Reticulum Protein, p180, Is Highly Expressed in Human Cytomegalovirus-Permissive Cells and Interacts with the Tegument Protein Encoded by UL48. J. Virol. 76: 2350-2362 [Abstract] [Full Text]  
  • Klupp, B. G., Fuchs, W., Granzow, H., Nixdorf, R., Mettenleiter, T. C. (2002). Pseudorabies Virus UL36 Tegument Protein Physically Interacts with the UL37 Protein. J. Virol. 76: 3065-3071 [Abstract] [Full Text]  
  • Mettenleiter, T. C. (2002). Herpesvirus Assembly and Egress. J. Virol. 76: 1537-1547 [Full Text]  
  • Dorange, F., Tischer, B. K., Vautherot, J.-F., Osterrieder, N. (2002). Characterization of Marek's Disease Virus Serotype 1 (MDV-1) Deletion Mutants That Lack UL46 to UL49 Genes: MDV-1 UL49, Encoding VP22, Is Indispensable for Virus Growth. J. Virol. 76: 1959-1970 [Abstract] [Full Text]  
  • Bechtel, J. T., Shenk, T. (2002). Human Cytomegalovirus UL47 Tegument Protein Functions after Entry and before Immediate-Early Gene Expression. J. Virol. 76: 1043-1050 [Abstract] [Full Text]  
  • Desai, P., Sexton, G. L., McCaffery, J. M., Person, S. (2001). A Null Mutation in the Gene Encoding the Herpes Simplex Virus Type 1 UL37 Polypeptide Abrogates Virus Maturation. J. Virol. 75: 10259-10271 [Abstract] [Full Text]  
  • Klupp, B. G., Granzow, H., Mundt, E., Mettenleiter, T. C. (2001). Pseudorabies Virus UL37 Gene Product Is Involved in Secondary Envelopment. J. Virol. 75: 8927-8936 [Abstract] [Full Text]  
  • Kinchington, P. R., Fite, K., Seman, A., Turse, S. E. (2001). Virion Association of IE62, the Varicella-Zoster Virus (VZV) Major Transcriptional Regulatory Protein, Requires Expression of the VZV Open Reading Frame 66 Protein Kinase. J. Virol. 75: 9106-9113 [Abstract] [Full Text]