Adenovirus genome

Adenovirus genomes are linear, non-segmented double-stranded (ds) DNA molecules that are typically 26-46 Kbp long, containing 23-46 protein-coding genes.[1] The example used for the following description is Human adenovirus E, a mastadenovirus with a 36 Kbp genome containing 38 protein-coding genes.[2] While the precise number and identity of genes varies among adenoviruses, the basic principles of genome organization and the functions of most of the genes described in this article are shared among all adenoviruses.

Transcription unitsEdit

 
Transcription units (in green) and genes (protein-coding genes in red, other genes in blue) of human adenovirus E genome

The 38 genes in the Human adenovirus E genome are organized in 17 transcription units, each containing 1-8 coding sequences.[3] Alternative splicing during processing of the pre-mRNAs produced by each transcription unit enable multiple different mRNAs to be produced from one transcription unit.

The E1A, E1B, E2A, E2B, E3, and E4 transcription units are successively transcribed early in the viral reproductive cycle. The proteins coded for by genes within these transcription units are mostly involved in regulation of viral transcription, in replication of viral DNA, and in suppression of the host response to infection.[4]

The L1-L5 transcription units are transcribed later in the viral reproductive cycle, and code mostly for proteins that make up components of the viral capsid or are involved in assembly of the capsid. The L1-L5 transcription units are all regulated by the same promoter region and share the same transcription start site. As a result, transcription of all five late transcription units begins at the same point in the viral reproductive cycle.[5]

Transcription of pre-mRNAs beginning at the late promoter is randomly terminated at one of five termination sites, producing a population of transcripts of five different lengths. The pre-mRNAs of any given length are then alternatively spliced to produce 1-4 different mRNAs coding for a corresponding number of proteins.

Protein-coding genesEdit

The names, locations, and properties of the 38 protein-coding genes in the Human Adenovirus E genome are given in the following table.[6][7]

Protein name Protein identifier Transcription unit Start base Stop base Strand Length (amino acids)
control protein E1A YP_068018.1 E1A 576 1441 + 257
control protein E1B 19K YP_068019.1 E1B 1600 2115 + 171
control protein E1B 55K YP_068020.1 E1B 1905 3356 + 483
capsid protein IX YP_068021.1 IX 3441 3869 + 142
encapsidation protein IVa2 YP_068022.1 IVa2 3930 5554 - 448
DNA polymerase YP_068023.1 E2B 5033 13773 - 1193
protein 13.6K YP_001661328.1 L1 7814 9476 + 139
terminal protein precursor pTP YP_068024.1 E2B 8404 13773 - 642
encapsidation protein 52K YP_068025.1 L1 10765 11937 + 390
capsid protein precursor pIIIa YP_068026.1 L1 11961 13736 + 591
penton base (capsid protein III) YP_068027.1 L2 13815 15422 + 535
core protein precursor pVII YP_068028.1 L2 15426 16007 + 193
core protein V YP_068029.1 L2 16055 17080 + 341
core protein precursor pX YP_068030.1 L2 17103 17336 + 77
capsid protein precursor pVI YP_068031.1 L3 17413 18141 + 242
hexon (capsid protein II) YP_068032.1 L3 18248 21058 + 936
protease YP_068033.1 L3 21082 21702 + 206
single-stranded DNA-binding protein YP_068034.1 E2A-L 21774 23312 - 512
hexon assembly protein 100K YP_068035.1 L4 23341 25716 + 791
protein 33K YP_068036.1 L4 25439 26252 + 214
encapsidation protein 22K YP_068037.1 L4 25439 25978 + 179
capsid protein precursor pVIII YP_068038.1 L4 26321 27004 + 227
control protein E3 12.5K YP_068039.1 E3 27005 27325 + 106
membrane glycoprotein E3 CR1-alpha YP_068040.1 E3 27279 27911 + 210
membrane glycoprotein E3 gp19K YP_068041.1 E3 27893 28417 + 174
membrane glycoprotein E3 CR1-beta YP_068042.1 E3 28449 29111 + 220
membrane glycoprotein E3 CR1-delta YP_068043.1 E3 29440 30264 + 274
membrane protein E3 RID-alpha YP_068044.1 E3 30273 30548 + 91
membrane protein E3 RID-beta YP_068045.1 E3 30554 30994 + 146
control protein E3 14.7K YP_068046.1 E3 30987 31388 + 133
protein U YP_068047.1 U 31481 31632 - 50
fiber (capsid protein IV) YP_068048.1 L5 31649 32926 + 425
control protein E4orf6/7 YP_068049.1 E4 33022 34169 - 141
control protein E4 34K YP_068050.1 E4 33270 34169 - 299
control protein E4orf4 YP_068051.1 E4 34072 34440 - 122
control protein E4orf3 YP_068052.1 E4 34449 34802 - 117
control protein E4orf2 YP_068053.1 E4 34799 35188 - 129
control protein E4orf1 YP_068054.1 E4 35236 35610 - 124

The functions of many adenovirus proteins are known:[5]

  • Structural proteins include capsid proteins II (hexon), III (penton base), IIIa, IV (fiber), VI, VIII, and IX; and core proteins V, VII, X, and the terminal protein TP.
  • Encapsidation proteins IVa2, 52K, and L1, and hexon assembly protein 100K are involved in assembly of viral capsids.
  • The L3 protease cleaves viral precursor proteins pTP, pVI, pVII, pVIII, and IIIa to produce the mature viral proteins.
  • Control protein E1A activates transcription of a number of viral genes as well as genes of the host cell.
  • Control protein E1B 19K suppresses apoptosis by mimicking the action of cellular protein Bcl-2.
  • Control protein E1B 55K binds to and inactivates the transcriptional regulator p53, thus blocking transcription of genes normally activated by p53 and contributing to the suppression of apoptosis.
  • The three proteins coded for by the E2A and E2B transcription units are all involved in replication of viral DNA. Adenovirus DNA replication begins at each end of the viral DNA, using the TP protein (rather than RNA) as a primer, so the viral DNA polymerase replicates every base of the genome.
  • Membrane protein E3 RID-alpha and membrane protein E3 RID-beta performs a variety of molecular functions that contribute to inhibiting apoptosis.[8]
  • CR1 beta membrane glycoprotein modulates the host immune response.[9]
  • Membrane glycoprotein E3 gp19K inhibits the insertion of class I MHC proteins in the host-cell membrane, thereby preventing T-cell lymphocytes from recognizing that the host cell has been infected by a virus.[10]
  • Control protein E3 14.7K protects the virus from host antiviral responses.[11]
  • The control proteins of the E4 transcription unit are involved in regulating transcription of viral DNA.[12]

ReferencesEdit

  1. ^ "Viruses – Complete Genomes". NCBI. Retrieved 2013-01-17.
  2. ^ "Human Adenovirus E Genome". NCBI. Retrieved 2013-01-17.
  3. ^ "Human adenovirus E overview". NCBI. Retrieved 2013-01-17.
  4. ^ "Adenoviruses". MicrobiologyBytes. Archived from the original on 2013-04-20. Retrieved 2013-01-17.
  5. ^ a b Branton, Philip; Marcellus, Richard C. (2011). "23". In Nicholas H. Acheson (ed.). Adenoviruses. Fundamentals of Molecular Virology (2 ed.). John Wiley & Sons, Inc.
  6. ^ "Protein Details for Human adenovirus E". NCBI. Retrieved 2013-01-17.
  7. ^ Russell, WC (Jan 2009). "Adenoviruses: update on structure and function". Journal of General Virology. 90 (Pt 1): 1–20. doi:10.1099/vir.0.003087-0. PMID 19088268. Archived from the original on 2014-10-31. Retrieved 2013-01-17.
  8. ^ "PHA3612: receptor internalization and degradation protein alpha". NCBI. Retrieved 2013-01-17.
  9. ^ "PHA3620: CR1 beta membrane glycoprotein". NCBI. Retrieved 2013-01-17.
  10. ^ "PHA3615: E3 gp19K protein". NCBI. Retrieved 2013-01-17.
  11. ^ "PHA3613: E3 14.7K protein". NCBI. Retrieved 2013-01-17.
  12. ^ "PHA3605: control protein E4orf4". NCBI. Retrieved 2013-01-17.