Marek’s Disease Virus (MDV) is a highly infectious lymphotropic alphaherpesvirus of poultry that induces Marek’s disease (MD), characterised by immunosuppression, paralysis and rapid-onset visceral lymphomas of the CD4+ T cells. MDV has a global distribution causing huge economic losses worldwide. MD remains a major concern for the poultry industry due to the unpredictability of outbreaks and the evolution of more virulent strains of MDV 1. As per the International Committee on Taxonomy of Viruses (ICTV) classification (http://www.ictvonline.org/virusTaxonomy.asp?version=2009), MDV belongs to the genus Mardivirus that comprises Gallid herpesvirus 2 (also called MDV1/serotype 1), Gallid herpesvirus 3 (MDV2/serotype 2) and Meleagrid herpesvirus 1 (Herpesvirus of turkey (HVT/ serotype 3). All the pathogenic viruses (and vaccine strains such as CVI988) belong to MDV1 species, while viruses belonging to MDV2 and HVT are all attenuated viruses used as vaccines against MD 2. On the basis of their virulence, MDV1 strains are further divided into mild (mMDV), virulent (vMDV), very virulent (vvMDV), and very virulent plus (vv+MDV) pathotypes 3. MDV enveloped particles range in size from 150-160 nm in diameter in cell culture, while structures measuring 273-400 nm have been detected in the feather follicle epithelial cells 4,5. The approximately 160-180kb double-stranded genome of MDV consists of unique long (UL) and unique short (US) regions flanked by internal (IRL and IRS) and terminal (TRL and TRS) repeats 6,7. The MDV genome encodes open reading frames (ORFs) that include both herpesvirus homologues, such as the glycoproteins gB, gC, gD, gE and gH, and unique genes, such as Meq and pp38 8,9. Additionally, MDV also encodes unique sets of non-coding RNAs that include microRNAs 4 and the telomerase RNA subunit 10,11, some of which are crucial for virus pathogenesis 12,13.
MDV infection is initiated by inhalation of infected dust and early infection is thought to occur in the macrophages in the lungs 14. Early cytolytic infection, lasting approximately a week, involves lymphocytes and macrophages and results in severe immunosuppression, thymic and bursal atrophy. In birds without maternal antibodies, such early cytolytic disease can also result in high mortality. After this period, MDV infection goes into a latency phase within the CD4+ and CD8+ T cells for the rest of the life of the infected birds. From around 10-days after infection, lytic replication of the virus can be observed in the feather follicle epithelium, from where infectious cell-free virus is shed into the poultry house environment for long periods of time, acting as a source of infection to naïve, newly introduced birds. In genetically susceptible unvaccinated birds, due to mechanisms still not fully understood, some of the latently-infected CD4+ T-cells are neoplastically transformed resulting in the development of T-cell lymphomas in multiple visceral organs. In some of these birds, lymphoid infiltration of peripheral nerves leads to paralytic symptoms. MD-associated mortality, due to neoplastic lesions and paralysis in birds from 3-4 week onwards, can cause serious economic losses. Vaccination or genetic resistance has very little effect on MDV life cycle and virus shedding.
MD is recognized as a major disease in all poultry producing countries. MDV is a highly successful pathogen capable of surviving for long periods within the infected hosts as well as in the poultry house environment. MD is restricted to avian species and has been reported in chickens, quail, turkeys and pheasants. MDV is transmitted readily by direct or indirect contact by the airborne route. The feather follicle epithelial cells from the infected birds, shed as dander, and dust are the main source of the virus. In commercial conditions, young birds placed into the poultry houses get infected from the residual dust and dander in the growing houses. Poultryhouse dust is a good source for detection of MDV genome copies and monitoring of infection at the flock level 15.
One important point to be borne in mind about MD diagnosis is that MDV is ubiquitous in many poultry farms and the detection of virus, viral antigens or nucleic acids alone in the absence of disease does not confirm the occurrence of MD. Macroscopic lesions of tumours and enlargement of peripheral nerves together with histopathological confirmation is commonly used in the diagnosis. Confirmatory laboratory diagnosis can be achieved by different assays including virus isolation on cell culture systems such as chicken/duck embryo fibroblasts and chicken kidney cells. More recently, PCR-based molecular diagnostic tests are more widely used than virus isolation. Availability of the nucleotide sequences of a number of pathogenic and vaccine strains of MDV have enabled the development of efficient PCR methods for precise detection and quantitation of pathogenic and vaccine strains.
Control of MD
Because of the ubiquitous nature of the virus with the potential for long term survival both within and outside the host, vaccination is the only effective strategy for the control of MD, although additional measures of increased biosecurity and selecting for genetic resistance are considered valuable adjuncts to the control programme. Several different types of MD vaccines are in use, both individually and in combinations. These include the HVT strain FC126, MDV-2 strain SB-1 and the MDV-1 strain CVI988, all of which have different levels of protective effects against MDV pathotypes of varying virulence. HVT is extensively used in broiler population, and is available both in cell-associated and cell-free forms 2. Bivalent vaccines, comprising HVT and SB-1, demonstrated improved protection through synergistic effects of the two vaccines. HVT virus is also extensively used as a live recombinant viral vector for protection against other avian pathogens 16,17. CVI988 strain is considered the most effective vaccine, and considered the gold standard in inducing protection, particularly against the more recent hypervirulent strains of MDV. MD vaccines are generally very effective, often inducing 90% or more protection under commercial conditions. However, their efficacy can vary with virulence of the MDV strains, and this forms the basis of the pathotyping assay to classify strains according to their virulence ranks to break though different vaccination regimes 3. Continuing increase in virulence of MDV strains in spite of vaccination is a major concern to the poultry industry 18. Recent study has demonstrated that the currently used MD vaccines such as HVT do contribute to increasing virulence by keeping the vaccinated hosts alive thereby encouraging transmission 1
Contributed by: Prof. Venugopal Nair
(The Pirbright Institute)
Copyright © 2016 Venugopal Nair
First posted: 13-Sept-2016
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