Comparative sequence analysis of A-type inclusion (ATI) and P4c proteins of orthopoxviruses that produce typical and atypical ATI phenotypes

Some orthopoxviruses produce large proteinaceous intracellular bodies, known as A-type inclusions (ATIs) during infection of host cells. Virions associate with ATIs resulting in distinct phenotypes referred to as V+, V+/ and V−. The phenotype V+ has the virions embedded in the ATI matrix; V− has no virions embedded within or on the surface of the ATI matrix, whereas an aberrant phenotype, the V+/ has virions only on the surface of ATIs. Viruses that do not produce ATI are designated as V0. Recombinant viruses generated from a V+ cowpox virus (CPXV) and a V0 transgenic vaccinia virus (VACV) produced aberrant V+/ ATIs. ATI phenotype is dependent on the A-type inclusion protein (Atip) and the P4c protein. We sequenced the atip and p4c genes of parental and progeny recombinant viruses as well as their flanking sequences. The atip and p4c open reading frames were identical in parental V+ CPXV and hybrid V+/ progenies. Our results suggest that additional viral gene(s) are required for the formation of wild type V+ ATI.

[1]  J. Marchal Infectious Ectromelia. A hitherto Undescribed Virus Disease of Mice. , 1930 .

[2]  A. Downie A study of the lesions produced experimentally by cowpox virus , 1939 .

[3]  Y. Ichihashi,et al.  Studies on the nature of Marchal bodies (A-type inclusion) during ectromelia virus infection. , 1966, Virology.

[4]  S Dales,et al.  Biogenesis of poxviruses: role of A-type inclusions and host cell membranes in virus dissemination. , 1971, Virology.

[5]  S. Dales,et al.  Biogenesis of poxviruses: relationship between a translation complex and formation of A-type inclusions. , 1973, Virology.

[6]  H. Shida,et al.  Mechanism of virus occlusion into A-type inclusion during poxvirus infection. , 1977, Virology.

[7]  P. Chang,et al.  Morphogenesis of canary poxvirus and its entrance into inclusion bodies. , 1985, American journal of veterinary research.

[8]  D. Patel,et al.  Isolation of cowpox virus A-type inclusions and characterization of their major protein component. , 1986, Virology.

[9]  D. Patel,et al.  Messenger RNAs of a strongly-expressed late gene of cowpox virus contain 5'-terminal poly(A) sequences. , 1987, The EMBO journal.

[10]  H. Rziha,et al.  Sequence alterations within and downstream of the A-type inclusion protein genes allow differentiation of Orthopoxvirus species by polymerase chain reaction. , 1994, The Journal of general virology.

[11]  B. Moss,et al.  A recombinant vector derived from the host range-restricted and highly attenuated MVA strain of vaccinia virus stimulates protective immunity in mice to influenza virus. , 1994, Vaccine.

[12]  D. Hruby,et al.  The vaccinia virus 4c and A-type inclusion proteins are specific markers for the intracellular mature virus particle , 1996, Journal of virology.

[13]  J. Thompson,et al.  The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. , 1997, Nucleic acids research.

[14]  H. Meyer,et al.  Gene for A-type inclusion body protein is useful for a polymerase chain reaction assay to differentiate orthopoxviruses , 1997, Journal of virological methods.

[15]  U. Moens,et al.  Characteristics of four cowpox virus isolates from Norway and Sweden , 1998, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[16]  F. Falkner,et al.  The complete genomic sequence of the modified vaccinia Ankara strain: comparison with other orthopoxviruses. , 1998, Virology.

[17]  B. Moss,et al.  Identification of Second-Site Mutations That Enhance Release and Spread of Vaccinia Virus , 2002, Journal of Virology.

[18]  D. Pickup,et al.  Identification of the Orthopoxvirus p4c Gene, Which Encodes a Structural Protein That Directs Intracellular Mature Virus Particles into A-Type Inclusions , 2002, Journal of Virology.

[19]  M. Law,et al.  Vaccinia virus motility. , 2003, Annual review of microbiology.

[20]  T. Traavik,et al.  Recombinant viruses obtained from co-infection in vitro with a live vaccinia-vectored influenza vaccine and a naturally occurring cowpox virus display different plaque phenotypes and loss of the transgene. , 2004, Vaccine.

[21]  T. Traavik,et al.  Modified vaccinia virus Ankara multiplies in rat IEC-6 cells and limited production of mature virions occurs in other mammalian cell lines. , 2006, The Journal of general virology.