Human Herpesvirus 2 (HSV-2)
  HSV-2 Genome and Proteome Properties  

INTRODUCTION

Human Herpesvirus 2 is the causative agent for genital herpes and disseminated neonatal herpes. With lower frequency HSV-2 can be isolated from labial, facial and ocular lesions. The complete genome sequence was published in 1998, "The Genome Sequence of Herpes Simplex Virus type 2" by Dolan, Jamieson, Cunningham, Barnett, and McGeoch, J Virol, March 1998, p. 2010-2021, Vol. 72, No. 3

GENOME STRUCTURE AND COORDINATE SYSTEM

The circular genome has 154,746 bp. HSV-1 and HSV-2 share the same overall structure, as well as very high similarity in most genes. Both HSV-1 and HSV-2 have two unique regions, named UL and US surrounded and defined by three sets of inverted repeats, named LTRa, LTRb and LTRc. The arrangement is shown below. The UL and US regions are found both in forward and inverted directions and wild type HSV occurs equally in all four possible arrangements (isomers) of the UL and US regions. The coordinate system is defined to begin at the first nucleotide of the shortest terminal repeat, LTRa, followed by LTRb, and the long unique region, UL, as shown in the diagram. The number of copies of the LTRa repeat may vary.

There are two origins of replication, OriL located within the UL region centered at 62,929 and OriS within repeat LTRc and LTRc' centered at 132,760 and 148,981.

HSV-2 TO HSV-1 GENOME COMPARISON

The BugSpray comparison below shows genome alignment based on similar genes and dramatically illustrates the similarity of gene arrangement between the HSV-1 and HSV-2 genomes. BugSpray draws lines from genes on the top genome, in this case HSV-2, to the gene with the best BLAST hit in the bottom genome, here HSV-1. Green lines indicate pairs of genes that code on the same strand and red lines indicate gene pairs that code on the opposite strand. Clearly there are no rearrangements or reordering of genes between these two viruses. The three red lines show best hits of gamma 34.5, alpha4 and alpha0 to the copy in the inverted repeat, because BugSpray arbitrarily selects only one best hit if there are multiple hits with the same weight. Only Orf-P does not have a BLASTp hit to a gene in the HSV-1 genome.

BUGSPRAY GENOME ALIGNMENT

CODON USAGE

Codon usage as determined by CodonW, written by John Peden pdxjfp@molbiol.ox.ac.uk, while in the laboratory of Paul Sharp at the University of Nottingham: 

Phe UUU  636 0.90 Ser UCU  159 0.36 Tyr UAU  187 0.36 Cys UGU  186 0.50
Leu UUA   41 0.06     UCA   58 0.13 TER UAA   25 0.90 TER UGA   32 1.16
    UUG  261 0.38     UCG  737 1.66     UAG   26 0.94 Trp UGG  500 1.00

    CUU  241 0.35 Pro CCU  187 0.19 His CAU  174 0.30 Arg CGU  210 0.32
    CUC 1098 1.59     CCC 2064 2.08     CAC  975 1.70     CGC 1974 3.01
    CUA  162 0.24     CCA  204 0.21 Gln CAA  172 0.27     CGA  269 0.41
    CUG 2332 3.38     CCG 1513 1.53     CAG 1086 1.73     CGG 1199 1.83

Ile AUU  158 0.42 Thr ACU   66 0.11 Asn AAU   93 0.21 Ser AGU  104 0.23
    AUC  872 2.31     ACC 1159 1.98     AAC  775 1.79     AGC  730 1.65
    AUA  104 0.28     ACA  113 0.19 Lys AAA  169 0.49 Arg AGA   74 0.11
Met AUG  693 1.00     ACG 1000 1.71     AAG  524 1.51     AGG  210 0.32

Val GUU  281 0.37 Ala GCU  215 0.14 Asp GAU  339 0.29 Gly GGU  237 0.27
    GUC 1182 1.55     GCC 3196 2.10     GAC 1976 1.71     GGC 1567 1.76
    GUA  150 0.20     GCA  222 0.15 Glu GAA  391 0.37     GGA  324 0.36
    GUG 1441 1.89     GCG 2441 1.61     GAG 1724 1.63     GGG 1443 1.62
43738 codons in 83 genes (used Universal Genetic code)

G+C CONTENT

The G+C content of the HSV-2 genome is 70.4%, compared with 68.3% for HSV-1. C+G content for each orf is listed here and graphed below. The three genes with the highest G+C content (>2 sigma) all lie within the long terminal repeats; gamma34.5 (81.7%), alpha4 (81.5%) and orf-P (within gamma34.5 at 80.3%). Genes with the lowest G+C content include UL1/gL (60.7%), UL55 (61.1%), US12 (62.4%), UL20 (63.4%), UL5 (63.6%) and UL3 (63.7%).

GENERAL FEATURES OF THE PROTEOME

Current analysis of this genome shows 79 distinct genes, 4 of which have two copies for a total of 83 genes. Three of these 79 genes have intron(s) and they are gamma34.5, alpha0 and UL15. Interestingly UL16and UL17code within the intron of UL15. Nine of the genes (11%) have been assigned an EC number while ten (13%) have unknown function.

Three pairs of genes are known to be coterminal and code in frame. These include: UL8.5 and UL9, UL15 and UL15.5 and UL26 and UL26.5.

Also three pairs of genes are known to overlap completely coding on opposite strands. They are: gamma34.5 and Orf-P, UL27.5 and UL27 and UL43 and UL43.5.

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Nina Thayer nthayer@lanl.gov
Last Modified: 10/01/2001