Skip to main content

Advertisement

SpringerLink
Log in

A-type inclusion bodies: a factor influencing cowpox virus lesion pathogenesis

  • Original Article
  • Published:
Archives of Virology Aims and scope Submit manuscript

Abstract

The family Poxviridae comprises the most complex animal DNA viruses. During some poxvirus infections, A-type inclusion bodies (ATIs), codified by the ati gene, are produced. Although some studies have compared poxviruses that encode these inclusion bodies with those that do not, the biological function of ATIs is poorly understood. A recombinant ati-deleted cowpox virus was constructed and compared with the wild-type virus in in vitro experiments including electron microscopy and plaque and viral growth assays. No significant differences were observed in vitro. This reinforces the conclusion that the inclusion body is not essential for in vitro viral replication and morphogenesis. Additionally, different lesion progressions in vivo were observed by macroscopic and histological analysis, suggesting that the presence or absence of ATIs could result in different healing dynamics. This is the first time that the role of ATIs during viral replication has been studied based solely on one variable, the presence or absence of ATIs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Amegadzie BY, Sisler JR, Moss B (1992) Frame-shift mutations within the vaccinia virus A-type inclusion protein gene. Virology 186:777–782

    Article  PubMed  CAS  Google Scholar 

  2. Butler-Cole C, Wagner MJ, Da Silva M, Brown GD, Burke RD, Upton C (2007) An ectromelia virus profilin homolog interacts with cellular tropomyosin and viral A-type inclusion protein. Virol J 4:76

    Article  PubMed  Google Scholar 

  3. Campos MAS, Kroon EG (1993) Critical period for reversible block of vaccinia virus replication. Rev Brasil Microbiol 24:104–110

    Google Scholar 

  4. da Fonseca FG, Moss B (2003) Poxvirus DNA topoisomerase knockout mutant exhibits decreased infectivity associated with reduced early transcription. Proc Natl Acad Sci USA 100:11291–11296

    Article  PubMed  CAS  Google Scholar 

  5. da Fonseca FG, Trindade GS, Silva RL, Bonjardim CA, Ferreira PCP, Kroon EG (2002) Characterization of a vaccinia-like virus isolated in a Brazilian forest. J Gen Virol 83:223–228

    PubMed  CAS  Google Scholar 

  6. da Fonseca FG, Wolffe EJ, Weisberg A, Moss B (2000) Characterization of the vaccinia virus H3L envelope protein: topology and posttranslational membrane insertion via the c-terminal hydrophobic tail. J Virol 74:7508–7517

    Article  PubMed  CAS  Google Scholar 

  7. da Fonseca FG, Wolffe EJ, Weisberg A, Moss B (2000) Effects of deletion or stringent repression of the H3L envelope gene on vaccinia virus replication. J Virol 74:7518–7528

    Article  PubMed  CAS  Google Scholar 

  8. Damon IK (2007) Poxviruses. In: Knipe DM, Howley PM (eds) Fields virology, 5th edn. Lippincott Williams & Wilkins, Philadelphia, pp 2947–2975

    Google Scholar 

  9. Davies DH, Molina DM, Wrammert J, Miller J, Hirst S, Mu Y, Pablo J, Unal B, Nakajima-Sasaki R, Liang X, Crotty S, Karem KL, Damon IK, Ahmed R, Villarreal L, Felgner PL (2007) Proteome-wide analysis of the serological response to vaccinia and smallpox. Proteomics 7:1678–1686

    Article  PubMed  CAS  Google Scholar 

  10. de Souza Trindade G, da Fonseca FG, Marques JT, Nogueira ML, Mendes LC, Borges AS, Peiró JR, Pituco EM, Bonjardim CA, Ferreira PC, Kroon EG (2003) Araçatuba virus: a vaccinia-like virus associated with infection in humans and cattle. Emerg Infect Dis 9:155–160

    PubMed  Google Scholar 

  11. Dvoracek B, Shors T (2003) Construction of a novel set of transfer vectors to study vaccinia virus replication and foreign gene expression. Plasmid 49:9–17

    Article  PubMed  CAS  Google Scholar 

  12. Earl PL, Moss B, Wyatt LS, Carroll MW (1998) Generation of recombinant vaccinia viruses. In: Ausubel FM, Brent R, Kingston RE, Moore DD, Seidman JG, Smith JA, Struhl K (eds) Current protocols in molecular biology, 1st edn. Wiley, New York, pp 16.17.1–16.17.19

    Google Scholar 

  13. Esposito JJ, Knight JC (1985) Orthopoxvirus DNA: a comparison of restriction profiles and maps. Virology 143:230–251

    Article  PubMed  CAS  Google Scholar 

  14. Fenner F (2002) Poxviruses. In: Richman DD, Whitley R, Hayden FG (eds) Clinical Virology, 2nd edn. American Society for Microbiology Press, Washington, DC, pp 359–374

    Google Scholar 

  15. Ferreira JM, Drumond BP, Guedes MIMC, Pascoal-Xavier MA, Almeida-Leite CM, Arantes RM, Mota BE, Abrahão JS, Alves PA, Oliveira FM, Ferreira PCP, Bonjardim CA, Lobato ZIP, Kroon EG (2008) Virulence in murine model shows the existence of two distinct populations of Brazilian Vaccinia virus strains. PLoS One 3:e3043

    Article  PubMed  Google Scholar 

  16. Fonseca FG, Lanna MC, Campos MA, Kitajima EW, Peres JN, Golgher RR, Ferreira PCP, Kroon EG (1998) Morphological and molecular characterization of the poxvirus BeAn 58058. Arch Virol 143:1171–1186

    Article  PubMed  CAS  Google Scholar 

  17. Funahashi S, Sato T, Shida H (1988) Cloning and characterization of the gene encoding the major protein of the A-type inclusion body of cowpox virus. J Gen Virol 69:35–47

    Article  PubMed  CAS  Google Scholar 

  18. Howard AR, Weisberg AS, Moss B (2010) Congregation of orthopoxvirus virions in cytoplasmic A-type inclusions is mediated by interactions of a bridging protein (A26p) with a matrix protein (ATIp) and a virion membrane-associated protein (A27p). J Virol 84:7592–7602

    Article  PubMed  CAS  Google Scholar 

  19. Ichihashi Y, Dales S (1973) Biogenesis of poxviruses: relationship between a translation complex and formation of A-type inclusions. Virology 51:297–319

    Article  PubMed  CAS  Google Scholar 

  20. Ichihashi Y, Matsumoto S (1966) Studies on the nature of Marchal bodies (A-type inclusion) during ectromelia virus infection. Virology 29:264–275

    Article  PubMed  CAS  Google Scholar 

  21. Ichihashi Y, Matsumoto S, Dales S (1971) Biogenesis of poxviruses: role of A-type inclusions and host cell membranes in virus dissemination. Virology 46:507–532

    Article  PubMed  CAS  Google Scholar 

  22. Joklik WK (1962) The purification of four strains of poxvirus. Virology 18:9–18

    Article  PubMed  CAS  Google Scholar 

  23. Knight JC, Goldsmith CS, Tamin A, Regnery RL, Regnery DC, Esposito JJ (1992) Further analyses of the orthopoxviruses volepox virus and raccoon poxvirus. Virology 190:423–433

    Article  PubMed  CAS  Google Scholar 

  24. Kochneva G, Kolosova I, Maksyutova T, Ryabchikova E, Shchelkunov S (2005) Effects of deletions of kelch-like genes on cowpox virus biological properties. Arch Virol 150:1857–1870

    Article  PubMed  CAS  Google Scholar 

  25. Leite JA, Drumond BP, Trindade GS, Bonjardim CA, Ferreira PCP, Kroon EG (2007) Brazilian Vaccinia virus strains show genetic polymorphism at the ati gene. Virus Genes 35:531–539

    Article  PubMed  CAS  Google Scholar 

  26. Leite JA, Drumond BP, Trindade GS, Lobato ZI, da Fonseca FG, dos SJ, Madureira MC, Guedes MI, Ferreira JM, Bonjardim CA, Ferreira PC, Kroon EG (2005) Passatempo virus, a vaccinia virus strain, Brazil. Emerg Infect Dis 11:1935–1938

    PubMed  Google Scholar 

  27. Marques JT, Trindade GS, da Fonseca FG, dos Santos JR, Bonjardim CA, Ferreira PCP, Kroon EG (2001) Characterization of ATI, TK and IFN-alpha/betaR genes in the genome of the BeAn 58058 virus, a naturally attenuated wild Orthopoxvirus. Virus Genes 23:291–301

    Article  PubMed  CAS  Google Scholar 

  28. Martin KH, Franke CA, Hruby DE (1999) Novel acylation of poxvirus A-type inclusion proteins. Virus Res 60:147–157

    Article  PubMed  CAS  Google Scholar 

  29. Mc Kelvey TA, Andrews SC, Miller SE, Ray CA, Pickup DJ (2002) Identification of the orthopoxvirus p4c gene, which encodes a structural protein that directs intracellular mature virus particles into A-type inclusions. J Virol 76:11216–11225

    Article  CAS  Google Scholar 

  30. Meyer H, Rziha HJ (1993) Characterization of the gene encoding the A-type inclusion protein of camelpox virus and sequence comparison with other orthopoxviruses. J Gen Virol 74:1679–1684

    Article  PubMed  CAS  Google Scholar 

  31. Meyer H, Pfeffer M, Rziha HJ (1994) Sequence alterations within and downstream of the A-type inclusion protein genes allow differentiation of Orthopoxvirus species by polymerase chain reaction. J Gen Virol 75:1975–1981

    Article  PubMed  CAS  Google Scholar 

  32. Meyer H, Roop SL, Esposito JJ (1997) Gene for A-type inclusion body proteins is useful for a polymerase chain reaction assay to differentiate orthopoxviruses. J Virol Methods 64:217–221

    Article  PubMed  CAS  Google Scholar 

  33. Moss B, Shisler JL (2001) Immunology 101 at poxvirus U: immune evasion genes. Seminol Immunol 13:59–66

    Article  CAS  Google Scholar 

  34. Moss B (2007) Poxviridae: the viruses and their replication. In: Knipe DM, Howley PM (eds) Fields virology, 5th edn. Lippincott Williams & Wilkins, Philadelphia, pp 2906–2931

    Google Scholar 

  35. Okeke MI, Adekoya OA, Moens U, Tryland M, Traavik T, Nilssen O (2009) Comparative sequence analysis of A-type inclusion (ATI) and P4c proteins of orthopoxviruses that produce typical and atypical ATI phenotypes. Virus Genes 39:200–209

    Article  CAS  Google Scholar 

  36. Osterrieder N, Meyer H, Pfeffer M (1994) Characterization of the gene encoding the A-type inclusion body protein of mousepox virus. Virus Genes 8:125–135

    Article  PubMed  CAS  Google Scholar 

  37. Patel DD, Pickup DJ, Joklik WK (1986) Isolation of cowpox virus A-type inclusions and characterization of their major protein component. Virology 149:174–189

    Article  PubMed  CAS  Google Scholar 

  38. Perdiguero B, Lorenzo MM, Blasco R (2008) Vaccinia virus A34 glycoprotein determines the protein composition of the extracellular virus envelope. J Virol 82:2150–2160

    Article  PubMed  CAS  Google Scholar 

  39. Pfeffer M, Meyer H (2007) Poxvirus diagnostics. In: Mercer AM, Schmidt A, Weber O (eds) Poxviruses, 1st edn. Birkhäuser, Basel, pp 355–373

    Chapter  Google Scholar 

  40. Pickup DJ, Ink BS, Hu W, Ray CA, Joklik WK (1986) Hemorrhage in lesions caused by cowpox virus is induced by a viral protein that is related to plasma protein inhibitors of serine proteases. Proc Natl Acad Sci USA 83:7698–7702

    Article  PubMed  CAS  Google Scholar 

  41. Sadasiv EC, Chang PW, Gulka G (1985) Morphogenesis of canary poxvirus and its entrance into inclusion bodies. Am J Vet Res 46:529–535

    PubMed  CAS  Google Scholar 

  42. Smith GL, Vanderplasschen A, Law M (2002) The formation and function of extracellular enveloped vaccinia virus. J Gen Virol 83:2915–2931

    PubMed  CAS  Google Scholar 

  43. Trindade GS, da Fonseca FG, Marques JT, Diniz S, Leite JA, De Bodt S, Van der Peer Y, Bonjardim CA, Ferreira PCP, Kroon EG (2004) Belo Horizonte virus: a vaccinia-like virus lacking the A-type inclusion body gene isolated from infected mice. J Gen Virol 85:2015–2021

    Article  PubMed  CAS  Google Scholar 

  44. Trindade GS, Lobato ZI, Drumond BP, Leite JA, Trigueiro RC, Guedes MI, da Fonseca FG, dos Santos JR, Bonjardim CA, Ferreira PC, Kroon EG (2006) Short report: isolation of two vaccinia virus strains from a single bovine vaccinia outbreak in rural area from Brazil: implications on the emergence of zoonotic orthopoxviruses. Am J Trop Med Hyg 75:486–490

    PubMed  CAS  Google Scholar 

  45. Tscharke DC, Smith GL (1999) A model for vaccinia virus pathogenesis and immunity based on intradermal injection of mouse ear pinnae. J Gen Virol 80:2751–2755

    PubMed  CAS  Google Scholar 

  46. Tscharke DC, Reading PC, Smith GL (2002) Dermal infection with vaccinia virus reveals roles for virus proteins not seen using other inoculation routes. J Gen Virol 83:1977–1986

    PubMed  CAS  Google Scholar 

  47. Ulaeto D, Grosenbach D, Hruby DE (1996) The vaccinia virus 4c and A-type inclusion proteins are specific markers for the intracellular mature virus particle. J Virol 70:3372–3377

    PubMed  CAS  Google Scholar 

  48. Whitton JL, Oldstone MBA (2001) The immune response to viruses. In: Knipe DM, Howley PM (eds) Fields virology, 5th edn. Lippincott Williams & Wilkins, Philadelphia, pp 285–320

    Google Scholar 

  49. Wilgus TA (2008) Immune cells in the healing skin wound: influential players at each stage of repair. Pharmacol Res 58:112–116

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We gratefully thank Angela S. Lopes, Ilda M. V. Gamma, and colleagues from the Virus Laboratory. Financial support for this work was provided by grants from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), and Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG). FGF, GST, RMEA, CAB, PCPF and EGK are CNPq fellows.

Author information

Author notes

  1. Juliana Almeida Leite

    Present address: EMBRAPA Gado de Leite (Brazilian Agriculture and Livestock Research Corporation/EMBRAPA Dairy Cattle), Rua Eugênio do Nascimento, 610 Dom Bosco, Juiz de Fora, MG, 36.038-330, Brazil

  2. Flávio Guimarães da Fonseca

    Present address: Laboratório de Virologia Comparada, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Belo Horizonte, MG, 31270-901, Brazil

  3. Camila Megale de Almeida-Leite

    Present address: Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Belo Horizonte, MG, 31270-901, Brazil

Authors and Affiliations

  1. Laboratório de Vírus, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, caixa postal 486, Belo Horizonte, MG, 31270-901, Brazil

    Juliana Almeida Leite, Flávio Guimarães da Fonseca, Giliane de Souza Trindade, Jônatas Santos Abrahão, João Rodrigues dos Santos, Maria Isabel Maldonado Coelho Guedes, Cláudio Antônio Bonjardim, Paulo César Peregrino Ferreira & Erna Geessien Kroon

  2. Laboratório de Neuro-Imuno Patologia Experimental, Departamento de Patologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Belo Horizonte, MG, 31270-901, Brazil

    Rosa Maria Esteves Arantes & Camila Megale de Almeida-Leite

  3. Departamento de Biologia Celular, Instituto de Ciências Biológicas, Universidade de Brasília, Asa Norte, Brasília, DF, 70910-900, Brazil

    Bergmann Morais Ribeiro

Authors
  1. Juliana Almeida Leite
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Flávio Guimarães da Fonseca
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Giliane de Souza Trindade
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jônatas Santos Abrahão
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rosa Maria Esteves Arantes
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Camila Megale de Almeida-Leite
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. João Rodrigues dos Santos
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Maria Isabel Maldonado Coelho Guedes
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Bergmann Morais Ribeiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Cláudio Antônio Bonjardim
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Paulo César Peregrino Ferreira
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Erna Geessien Kroon
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Erna Geessien Kroon.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Leite, J.A., da Fonseca, F.G., de Souza Trindade, G. et al. A-type inclusion bodies: a factor influencing cowpox virus lesion pathogenesis. Arch Virol 156, 617–628 (2011). https://doi.org/10.1007/s00705-010-0900-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00705-010-0900-0

Keywords

Search

Navigation