Replication ability of three highly protective Marek's disease vaccines: implications in lymphoid organ atrophy and protection

Abstract

The present work is a chronological study of the pathogenesis of three attenuated serotype 1 Marek's disease (MD) virus strains (RM1, CVI988 and 648A80) that provide high protection against MD but have been attenuated by different procedures and induce different degrees of lymphoid organ atrophy. All studied strains replicated in the lymphoid organs (bursa,x thymus and spleen) and a peak of replication was detected at 6 days post inoculation (d.p.i.). Differences, however, were observed among vaccine strains. RM1 strain replicates more in all lymphoid organs compared with CVI988 and 648A80 strains. In addition, replication of RM1 in the thymus did not decrease after 6 d.p.i. but continued at high levels at 14 d.p.i. and until the thymus was completely destroyed. Lung infection occurred very early after infection with all of the three vaccines and the level of replication was similar to that found in the lymphoid organs. Infected cells were very large and appeared scattered in the lung parenchyma and in the parabronchial lining. The study of the target cells for the early infection in cell suspensions of blood and spleen showed that both non-adherent cell populations (enriched in lymphoid cells) and adherent cells (enriched in monocytes/macrophages) supported MD virus infection. Infection in adherent cells was especially high at very early stages of the infection (3 to 6 d.p.i.). Atrophy of lymphoid organs is a major drawback in the production of highly protective vaccines against MD. A better understanding of the mechanisms associated with lymphoid organ atrophy will aid in overcoming this problem.

Vaccination and Host Marek's Disease-Resistance Genotype Significantly Reduce Oncogenic <b><i>Gallid alphaherpesvirus 2</i></b> Telomere Integration in Host Birds

“…The genomes of these strains are highly similar to the oncogenic strains, but crucial differences exist . The MD vaccine viruses replicate in host cells and transmit to other birds [Baigent et al, 2005;Islam et al, 2007;Tan et al, 2007;Gimeno et al, 2011;Islam et al, 2013;], but do not induce disease or lymphomas [Calnek and Witter, 1997]. Despite improved understanding of vaccine-related immunity [Witter, 1984;Osterrieder et al, 2006], an explanation for the anti-tumor effect of vaccination has not yet been established.…”

“…In the MDV infection cycle, oncogenic strains transition from a cytolytic replication stage, during which the viral genome takes an episomal and extrachromosomal form, to a latent stage, characterized by evasion of host immune responses Adldinger and Calnek, 1973;Baigent and Davison, 2004;Osterrieder et al, 2006;Arumugaswami et al, 2009;Gimeno et al, 2011] with the latter having a temporal overlap with MDV-host telomere integration events [Robinson et al, 2010[Robinson et al, , 2014 and decline in the quantity of extrachromosomal MDV genomes [Kaschka-Dierich et al, 1979;Delecluse and Hammerschmidt, 1993]. Latently infected host CD4 T lymphocytes are the target cell population for transformation events and subsequent lymphoma development, around 2-3 weeks after infection in susceptible birds [Witter, 1984;Calnek, 2001;Burgess and Davison, 2002;Nair, 2005;Trapp et al, 2006].…”

Cytokines Evaluation of Different Mareks Disease Virus Vaccines in Broiler Chickens

“…Therefore, the non-oncogenic HVT may provoke higher IL-10 expression. Meanwhile, the proposed higher replication of Rispens strain over the HVT one in the thymus tissue as suggested by Gimeno et al, (2011) may provide an explanation for the non-significant difference in IL-10 expression in the thymus.…”

“…Gimeno et al, (2011) showed that the CVI988 strain replicates in the bursa and thymus and its viral DNA can be detected in those organs by the day 6 post s/c inoculation, then this replication decline toward the day 14 followed by a second replication wave as recorded in their following examination time point at 26 days. Their results also revealed that CVI-988 viral DNA load in thymus was higher than in bursa.…”

Addition of a UL5 helicase-primase subunit point mutation eliminates bursal–thymic atrophy of Marek's disease virus ∆Meq recombinant virus but reduces vaccinal protection

“…RM1 was determined to be attenuated and replicated efficiently in vivo, yet failed to cause MD and was typified by severe BTA (Jones et al, 1996). Further characterization revealed that not only was the attenuated RM1 virus very protective as a vaccine, but also exhibited high tissue tropism for early dissemination and replication to the thymus (Gimeno et al, 2011). Among several vaccine viruses examined, RM1 showed the earliest and highest replication within lymphoid organs, specifically the thymus, compared to the vaccine viruses that did not cause BTA.…”