Models of Virus-Induced Carcinogenesis and Oncolytic Viruses.

Avariety of infectious agents have been linked to cancer. Viruses, bacteria, and parasites have been linked to tumors in animals and humans. Viruses associated with cancer formation cause alteration of physiologic control of cell growth and proliferation or may increase the susceptibility of the host to other cancer risk factors such as environmental toxins. The study of virus–cell interactions has provided fundamental knowledge of cell biology and cell transformation. Viruses associated with cancer and model systems to study these mechanisms have established basic paradigms for virus–cell interactions and contributed greatly to the understanding of diseases associated with biomedically important viruses. More recently, some viruses, the so-called oncolytic viruses, have been used as agents against cancer. This background was the motivation and rationale for dedicating an entire issue of the ILAR Journal to models of virus-induced carcinogenesis and oncolytic viruses. The discovery of feline immunodeficiency virus (FIV) as a naturally occurring retrovirus, first in domestic cats and later in nondomestic feline species, allowed the comparative study of this lentivirus as a model of HIV-1 infection and disease. The ability to study the natural infection in feline species, which exhibit immune regulation similar to humans, has established this animal model as an important system to test hypotheses related to lentivirus disruption of immune control and subsequent pathologic outcomes. Sharing similar rates of neoplasia associated with both FIV and HIV infections, the comparative study of these viruses allow parallel studies to understand underlying factors that account for how lentivirusesmaypromote cancer formation. The review by Kaye and colleagues (2016) provides insights into current evidence on how FIV may promote the development of lymphoma in infected cats and the role of co-infections by other natural pathogens in tumor induction. Among these co-infections, the authors explore the role of feline gamma-herpes virus as a contributing factor to disease in infected cats and in retrovirus latency. The authors detail in their article the need for further evaluation of unique genetic elements of these viral pathogens and the influence of co-infections in disease outcomes. In addition, the authors discuss unique opportunities to use naturally infected animal populations from geographically disperse regions to test hypotheses around lentivirus-associated carcinogenesis. One of the earliest viruses associated with cancer was mouse mammary tumor virus (MMTV), which has served as a model of retroviral transmission and in investigations seeking to understand how the antiviral immune response influences the incidence of cancer. The review in this issue by Dudley and colleagues (2016) outlines some of the lessons learned from MMTV. It includes recent studies that have determined the interplay between key target cells and the immune system that characterizes the infection and pathogenic outcomes. Unique mechanisms of immune evasion are used by MMTV to allow for viral transmission and ultimately cellular oncogene expression. This model system has provided fundamental knowledge of how oncogenes disrupt cellular growth and continues to shed light on how retroviruses evade immune elimination. Also, in this issue, rodentmodels to evaluate oncolytic viruses as therapeutic agents are reviewed by Speranza and colleagues (2016). The use of viruses as anticancer agents has been evaluated in clinical trials in humans for more than 20 years and oncolytic viruses have emerged as viable therapeutic agents over the past decade. This review compares the range of viruses used as therapeutic agents and the evidence for those that are most promising. The review illustrates rodentmodels used to evaluate the preclinical efficacy of oncolytic viruses in context to the intrinsic ways these agents target cancer cells and achieve antitumor effects. The recent documentation of a successful phase III