The products of human cytomegalovirus genes UL23, UL24, UL43 and US22 are tegument components

Adair, Richard; Douglas, Elaine; Maclean, Jean B.; Graham, Susan Y.; Aitken, J D; Jamieson, Fiona E.; Dargan, Derrick J.

doi:10.1099/0022-1317-83-6-1315

Cited by 44 publications

(25 citation statements)

References 35 publications

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“…Nine of these HCMV-encoded polypeptides (UL38, UL50, UL71, UL79, UL93, UL96, UL102, US23, and US24) are required for efficient virus growth in cultured fibroblasts (12,43). UL4, UL23, UL53, UL56, UL98a, and US28 have previously been reported to be associated with HCMV particles (1,6,7,10,37). Although peptides corresponding to these viral proteins were detected in our study, the peptides failed to meet the criteria, as outlined in Materials and Methods, for inclusion in our database.…”

Section: Resultsmentioning

confidence: 99%

Identification of Proteins in Human Cytomegalovirus (HCMV) Particles: the HCMV Proteome

Varnum

Streblow

Monroe

et al. 2004

J Virol

529

350

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Human cytomegalovirus (HCMV), a member of the herpesvirus family, is a large complex enveloped virus composed of both viral and cellular gene products. While the sequence of the HCMV genome has been known for over a decade, the full set of viral and cellular proteins that compose the HCMV virion are unknown. To approach this problem we have utilized gel-free two-dimensional capillary liquid chromatography-tandem mass spectrometry (MS/MS) and Fourier transform ion cyclotron resonance MS to identify and determine the relative abundances of viral and cellular proteins in purified HCMV AD169 virions and dense bodies. Analysis of the proteins from purified HCMV virion preparations has indicated that the particle contains significantly more viral proteins than previously known. In this study, we identified 71 HCMV-encoded proteins that included 12 proteins encoded by known viral open reading frames (ORFs) previously not associated with virions and 12 proteins from novel viral ORFs. Analysis of the relative abundance of HCMV proteins indicated that the predominant virion protein was the pp65 tegument protein and that gM rather than gB was the most abundant glycoprotein. We have also identified over 70 host cellular proteins in HCMV virions, which include cellular structural proteins, enzymes, and chaperones. In addition, analysis of HCMV dense bodies indicated that these viral particles are composed of 29 viral proteins with a reduced quantity of cellular proteins in comparison to HCMV virions. This study provides the first comprehensive quantitative analysis of the viral and cellular proteins that compose infectious particles of a large complex virus.

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Section: Resultsmentioning

confidence: 99%

Identification of Proteins in Human Cytomegalovirus (HCMV) Particles: the HCMV Proteome

Varnum

Streblow

Monroe

et al. 2004

J Virol

529

350

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“…6 demonstrate the presence of motif III (part of pfam02393) in all previously identified HCMV US22 proteins and also in the UL26 protein. The UL26 protein is a component of the virion tegument (Baldick & Shenk, 1996;Stamminger et al, 2002), as are other US22 proteins (Adair et al, 2002), and contains a transcriptional activation domain (Stamminger et al, 2002). Until now, US22 motifs have not been found outside the Betaherpesvirinae, but we have identified motif III in several other viruses from the Herpesviridae, Poxviridae and Adenoviridae (Fig.…”

Section: Gene Content Of Ccmv and Hcmvmentioning

confidence: 99%

The human cytomegalovirus genome revisited: comparison with the chimpanzee cytomegalovirus genome FN1

Davison¹,

Dolan²,

Akter³

et al. 2003

Journal of General Virology

Self Cite

363

229

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The gene complement of wild-type human cytomegalovirus (HCMV) is incompletely understood, on account of the size and complexity of the viral genome and because laboratory strains have undergone deletions and rearrangements during adaptation to growth in culture. We have determined the sequence (241 087 bp) of chimpanzee cytomegalovirus (CCMV) and have compared it with published HCMV sequences from the laboratory strains AD169 and Toledo, with the aim of clarifying the gene content of wild-type HCMV. The HCMV and CCMV genomes are moderately diverged and essentially collinear. On the basis of conservation of potential proteincoding regions and other sequence features, we have discounted 51 previously proposed HCMV ORFs, modified the interpretations for 24 (including assignments of multiple exons) and proposed ten novel genes. Several errors were detected in the published HCMV sequences. We presently recognize 165 genes in CCMV and 145 in AD169; this compares with an estimate of 189 unique genes for AD169 made in 1990. Our best estimate for the complement of wild-type HCMV is 164 to 167 genes. INTRODUCTIONHuman cytomegalovirus (HCMV; human herpesvirus 5) is ubiquitous and largely inapparent, but poses a risk of serious disease to those lacking a competent immune system, such as neonates, transplant patients and sufferers from AIDS (reviewed in Pass, 2001). HCMV is the prototype of subfamily Betaherpesvirinae, and is the most complex of the eight human herpesvirus species. HCMV is isolated routinely on human fibroblast cell lines, and several strains in common laboratory use, such as AD169 and Towne, were derived by multiple passages on such cells (reviewed in Mocarski & Tan Courcelle, 2001).The linear, double-stranded DNA genome of AD169 comprises two covalently linked segments (L and S), each consisting of a unique region (U L and U S ) flanked by an inverted repeat (TR L and IR L , TR S and IR S ), yielding the overall genome configuration TR L -U L -IR L -IR S -U S -TR S (reviewed in Mocarski & Tan Courcelle, 2001). In addition, the genome is terminally redundant, possessing a short region (the a sequence) as a direct repeat at the termini and also in inverse orientation at the IR L -IR S junction. Some genomes contain tandemly reiterated copies of the a sequence at these locations. U L and U S can invert relative to each other by recombination between inverted repeats in replicating DNA, resulting in four equimolar genome arrangements in virion DNA. The complete DNA sequence of AD169 was published in a seminal paper by Chee et al. (1990), and at that time was the largest viral genome sequence available. The total genome size was 229 354 bp, with U L being 166 972 bp, U S 35 418 bp, R L (a collective term for TR L and IR L ) 11 247 bp, R S (TR S and IR S ) 2524 bp and the a sequence (part of R L and R S in the sizes given above) 578 bp.As a primary criterion for identifying protein-coding regions, Chee et al. (1990) focused on open reading frames (ORFs) of 100 or more contiguous amino acidencoding codons that ov...

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“…In addition to those described above (UL36, IRS1 [TRS1], and US24), other members of the US22 family, namely, UL23, UL24, UL43, US22, and US23, are also incorporated into virions (2,192). It is not known if additional members of the family (UL28, UL29, and US26) are virion proteins, but they are required for efficient viral replication (44,209).…”

Section: Other Tegument Proteinsmentioning

confidence: 99%

Tegument Proteins of Human Cytomegalovirus

Kalejta

2008

Microbiol Mol Biol Rev

162

149

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SUMMARY Human cytomegalovirus (HCMV) is a common, medically relevant human herpesvirus. The tegument layer of herpesvirus virions lies between the genome-containing capsids and the viral envelope. Proteins within the tegument layer of herpesviruses are released into the cell upon entry when the viral envelope fuses with the cell membrane. These proteins are fully formed and active and control viral entry, gene expression, and immune evasion. Most tegument proteins accumulate to high levels during later stages of infection, when they direct the assembly and egress of progeny virions. Thus, viral tegument proteins play critical roles at the very earliest and very last steps of the HCMV lytic replication cycle. This review summarizes HCMV tegument composition and structure as well as the known and speculated functions of viral tegument proteins. Important directions for future investigation and the challenges that lie ahead are identified and discussed.

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The products of human cytomegalovirus genes UL23, UL24, UL43 and US22 are tegument components

Cited by 44 publications

References 35 publications

Identification of Proteins in Human Cytomegalovirus (HCMV) Particles: the HCMV Proteome

Identification of Proteins in Human Cytomegalovirus (HCMV) Particles: the HCMV Proteome

The human cytomegalovirus genome revisited: comparison with the chimpanzee cytomegalovirus genome FN1

Tegument Proteins of Human Cytomegalovirus

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