Latest Insights into Marek's Disease Virus Pathogenesis and Tumorigenesis

Abstract

Marek's disease virus (MDV) infects chickens and causes one of the most frequent cancers in animals. Over 100 years of research on this oncogenic alphaherpesvirus has led to a profound understanding of virus-induced tumor development. Live-attenuated vaccines against MDV were the first that prevented cancer and minimized the losses in the poultry industry. Even though the current gold standard vaccine efficiently protects against clinical disease, the virus continuously evolves towards higher virulence. Emerging field strains were able to overcome the protection provided by the previous two vaccine generations. Research over the last few years revealed important insights into the virus life cycle, cellular tropism, and tumor development that are summarized in this review. In addition, we discuss recent data on the MDV transcriptome, the constant evolution of this highly oncogenic virus towards higher virulence, and future perspectives in MDV research.

Keywords: Marek’s disease virus; avian cancer; cell tropism; herpesvirus; life cycle; lymphoma; vaccine.

Figure 1

Marek’s disease virus (MDV) infection starts with the inhalation of infectious dust. Mononuclear phagocytes transfer the virus to lymphoid organs, such as the spleen, thymus, and bursa, where the virus lytically replicates in lymphocytes. MDV is able to establish latency in infected T cells. Latently and/or lytically infected T cells transport the virus to the skin and feather follicle epithelia (FFE), where cell free MDV is generated. In addition, MDV can transform latently infected T cells, resulting in deadly lymphomas.

Figure 2

Increasing average virulence of MDV field strains and introduction of the different MDV vaccines over the past decades in the USA (HVT, herpesvirus of turkey; SB1, Gallid herpesvirus 3 strain; CVI988,non-oncogenic MDV strain). The HVT vaccine was launched in the 1970s, the bivalent HVT+SB1 in the late 1980s and the current CVI988 vaccine in the 1990s (USA)/1970s (Europe) [14]. Symbols represent the different MDV pathotypes: m (blue), v (green), vv (orange), and vv+ (red). At the same time, breeding programs focused on an increased resistance to MDV-induced tumorigenesis.