The Genome of a Very Virulent Marek's Disease Virus

Abstract

Here we present the first complete genomic sequence, with analysis, of a very virulent strain of Marek's disease virus serotype 1 (MDV1), Md5. The genome is 177,874 bp and is predicted to encode 103 proteins. MDV1 is colinear with the prototypic alphaherpesvirus herpes simplex virus type 1 (HSV-1) within the unique long (UL) region, and it is most similar at the amino acid level to MDV2, herpesvirus of turkeys (HVT), and nonavian herpesviruses equine herpesviruses 1 and 4. MDV1 encodes 55 HSV-1 UL homologues together with 6 additional UL proteins that are absent in nonavian herpesviruses. The unique short (US) region is colinear with and has greater than 99% nucleotide identity to that of MDV1 strain GA; however, an extra nucleotide sequence at the Md5 US/short terminal repeat boundary results in a shorter US region and the presence of a second gene (encoding MDV097) similar to the SORF2 gene. MD5, like HVT, encodes an ICP4 homologue that contains a 900-amino-acid amino-terminal extension not found in other herpesviruses. Putative virulence and host range gene products include the oncoprotein MEQ, oncogenicity-associated phosphoproteins pp38 and pp24, a lipase homologue, a CxC chemokine, and unique proteins of unknown function MDV087 and MDV097 (SORF2 homologues) and MDV093 (SORF4). Consistent with its virulent phenotype, Md5 contains only two copies of the 132-bp repeat which has previously been associated with viral attenuation and loss of oncogenicity.Marek's disease (MD) is a lymphoproliferative disease of chickens caused by the highly infectious cell-associated alphaherpesvirus MD virus serotype 1 (MDV1) (18). Yearly economic losses from MD total $1 billion worldwide (18). MDV1 infection results in a rapid onset of malignant T-cell lymphomas within several weeks of infection. Tumor infiltration results in a neural form of disease, which causes progressive paralysis, or a visceral form of disease, which is usually very acute and accompanied by high mortality. Productive virus replication in the skin and feather follicle epithelia with subsequent virus shedding is responsible for disease transmission (18).MD is controlled by vaccination and good management practices (18). Naturally occurring nonpathogenic strains of MDV1, MDV2, and herpesvirus of turkey (HVT or MDV3) have been used individually or together in bivalent vaccines (18,40). Recent increases in MD-related mortality and condemnations among vaccinated poultry have occurred in the United States. These increases in disease have occurred approximately 6 years after the introduction of new vaccines (99). In the late 1970s, following the introduction of HVT vaccines, and since 1992, after the introduction of bivalent MDV2-HVTbased vaccines, new MDV1 strains of greater virulence (very virulent [vv] and very virulent plus [vv ϩ ] MDV1) were isolated. These viruses are characterized by higher cytolytic activity, unusual tissue tropism, increased atrophy of lymphoid organs, immunosuppression, enhanced capacity to transform T cells, and earlier host death (7...

Marek's disease virus-encoded Meq gene is involved in transformation of lymphocytes but is dispensable for replication

“…This extended deletion resulted in the loss of EcoRI site corresponding to position 7,100, and therefore, the 1,370-bp EcoRI fragment from the TR L migrated as a 5,063-bp fragment. Sequence analysis of this extended deletion indicated that no other large contiguous ORFs were deleted (14). However, because splicing and sense͞ antisense expression in this region is highly complex, it may affect gene expression.…”

A full UL13 open reading frame in Marek's disease virus (MDV) is dispensable for tumor formation and feather follicle tropism and cannot restore horizontal virus transmission of rRB-1B in vivo

“…Horizontal spread, thus far, is the only property lacking in rRB-1B to make it a full model to study MDV biology. Despite this shortcoming, pRB-1B and its derivatives are great tools to determine the molecular determinants involved in MDV horizontal dissemination in birds by individual, consequential or concomitant repair of genes that are found to be different from authentic, wild-type MDV [17,32].…”

“…The MDV genome is approximately 185 kbp in size and encodes at least 103 proteins [32]. Several MDV genomes have been cloned as bacterial artificial chromosomes, including an avirulent strain (584Ap80C) (yielding the bacmid BAC20) and the highly virulent strain RB-1B (yielding the bacmid pRB-1B) [21,26].…”

Applying the isothermal DNA amplification method in identifying the Marek’s disease virus in poultry

“…Wirus MDV z powodu swej limfotropowej natury początkowo klasyfikowany był jako Gammaherpesvirinae, jednak w 2002 r., po uzyskaniu pełnej sekwencji genomu nastąpiła jego reklasyfikacja do nowego rodzaju Mardivirus (41), w obrębie którego wyodrębniono jeszcze 4 inne gatunki, tj. : Gallid herpesvirus 3 (GaHV-3), Meleagrid herpesvirus 1 (MeHV-1) -znany także pod nazwą herpesvirus indyków (HVT), Anatid herpesvirus 1 i Columbid herpesvirus 1.…”