Chapter 15 : Genome Plasticity of Herpesviruses: Conservative yet Flexible

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Herpesvirus virions contain a double-stranded DNA (dsDNA) genome of 108 kbp (bovine herpesvirus 4) to 248.5 kbp (anguillid herpesvirus 1) in length. To date, eight different human herpesviruses (HHV) are known. Among human-pathogenic herpesviruses, human cytomegalovirus (HCMV) has the longest genome at ~230 kbp. Importantly, selected host proteins, such as actin, annexin, CD55, and CD59 become "deliberately" incorporated into herpesvirus particles as well. Based on virion morphology criteria, herpesviruses have been found in a variety of vertebrate classes, such as mammals, reptiles, fish, and birds, and even in invertebrates such as oysters. Herpesviruses are the only known viruses capable of deploying two separate transcriptional programs upon infection of a target cell: productive (and usually lytic) infection and latent infection. As observed in other DNA viruses like the Poxviridae, herpesviruses seem to steal genes from their host species and use them for their own purposes, a strategy called molecular piracy. Among herpesviruses, HHV-8 seems to be "the unchallenged master of molecular piracy". A section in the chapter explains leading genetic paradigms combined with selected findings from certain herpesviruses, to put the most important principles of herpesvirus genome plasticity and also their limitations into a broader perspective. The chapter presents examples that highlight the ability of herpesviruses to rapidly mutate under selecting conditions, indicating a remarkable potential of genetic plasticity and adaptability within a handful of in vivo passages.

Citation: Trilling M, Khanh Le V, Hengel H. 2012. Genome Plasticity of Herpesviruses: Conservative yet Flexible, p 248-266. In Hacker J, Dobrindt U, Kurth R (ed), Genome Plasticity and Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817213.ch15

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Herpes simplex virus 1
Viral Life Cycle
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Image of FIGURE 4

Phylogenetic trees based on alignments of primary amino acid sequences of the MCMV proteins pUL138 (A), pTRL12 (B), pUL139 (C), and pUL146 (D) indicate significant differences concerning variability of individual viral proteins, even at adjacent positions in the viral genome, like the ′ region. For all four proteins, all currently available protein sequences (status January 2011) from the NCBI server have been compared. The sequences of the homologous chimpanzee or rhesus CMV (CCMV or rhCMV, respectively) proteins serve as the outgroup. The alignment and phylogenetic tree were constructed with the www.phylogeny.fr online tool ( ). The legend depicts the protein sequence divergence. doi:10.1128/9781555817213.ch15f04

Citation: Trilling M, Khanh Le V, Hengel H. 2012. Genome Plasticity of Herpesviruses: Conservative yet Flexible, p 248-266. In Hacker J, Dobrindt U, Kurth R (ed), Genome Plasticity and Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817213.ch15
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Image of FIGURE 1

Model of herpesvirus virion morphology. The linear dsDNA genome is enclosed in the icosahedral capsid, which is surrounded by the proteinaceous tegument and embedded in the membrane envelope derived from the host cell. The virion membrane contains several virus-encoded as well as host-derived transmembrane proteins. doi:10.1128/9781555817213.ch15f01

Citation: Trilling M, Khanh Le V, Hengel H. 2012. Genome Plasticity of Herpesviruses: Conservative yet Flexible, p 248-266. In Hacker J, Dobrindt U, Kurth R (ed), Genome Plasticity and Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817213.ch15
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Image of FIGURE 2

Phylogenetic tree based on alignment of the primary amino acid sequences of DNA polymerases of the indicated herpesviruses demonstrates a relationship between the eight human-pathogenic herpesviruses (HSV-1, HSV-2, VZV, EBV, HCMV, HHV-6, HHV-7, and KSHV) and relevant animal herpesviruses(i.e. Marek's disease virus, pseudorabies virus, MHV-68, and MCMV). The sequence of the DNA polymerase delta serves as an outgroup. The alignment and phylogenetic tree were constructed using the www.phylogeny.fr online tool ( ). The legend depicts the protein sequence divergence. doi:10.1128/9781555817213.ch15f02

Citation: Trilling M, Khanh Le V, Hengel H. 2012. Genome Plasticity of Herpesviruses: Conservative yet Flexible, p 248-266. In Hacker J, Dobrindt U, Kurth R (ed), Genome Plasticity and Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817213.ch15
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Image of FIGURE 3

Comparative genomic organization and gene content of prototypic human herpesviruses, herpes simplex virus (top), human cytomegalovirus clinical isolates and laboratory strain AD169 (middle), and Epstein-Barr virus (bottom). For more detailed descriptions, see the text. and depict repetitive sequences of the L-terminal sequence ( ) or the S-terminal sequence ( ) and the L-terminal sequence, respectively, and their inverted repeats ′ and with zero to several or one to several copies. Additionally, the sequence and the inverted repeat ′ are shown. and ′ are synonymous with and , respectively, and and ′ are synonymous with and , respectively. Abbreviations: , terminal repeat long; , internal repeat long; , internal repeat short; , terminal repeat short; , unique long gene segment; , unique short gene segment; , terminal direct repeat; , internal direct repeat; , origin of lytic replication; (L), origin of lytic replication in L component (S1/2), origin of lytic replication in the S component , origin of plasmid replication; MIEP, major immediate-early promoter. doi:10.1128/9781555817213.ch15f03

Citation: Trilling M, Khanh Le V, Hengel H. 2012. Genome Plasticity of Herpesviruses: Conservative yet Flexible, p 248-266. In Hacker J, Dobrindt U, Kurth R (ed), Genome Plasticity and Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817213.ch15
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Selection of herpesviruses of nonhuman primates, mammals, birds, and fish

Citation: Trilling M, Khanh Le V, Hengel H. 2012. Genome Plasticity of Herpesviruses: Conservative yet Flexible, p 248-266. In Hacker J, Dobrindt U, Kurth R (ed), Genome Plasticity and Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817213.ch15
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Herpesviruses of humans

Citation: Trilling M, Khanh Le V, Hengel H. 2012. Genome Plasticity of Herpesviruses: Conservative yet Flexible, p 248-266. In Hacker J, Dobrindt U, Kurth R (ed), Genome Plasticity and Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817213.ch15

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