Autonomous Parvoviruses neither Stimulate nor Are Inhibited by the Type I Interferon Response in Human Normal or Cancer Cells

Abstract

Members of the genus IMPORTANCEUnderstanding the interactions between oncolytic viruses and the innate immune system will facilitate employing these viruses as therapeutic agents in cancer patients. The cancer-selective nature of some oncolytic viruses is based on the impaired innate immunity of many cancer cells. The parvoviruses H-1, LuIII, and MVM target cancer cells; however, their relationship with the innate immune system is relatively uncharacterized. Surprisingly, we found that these parvoviruses do not evoke an interferon response in normal human fibroblasts, glia, or melanocytes. Furthermore, unlike most other types of virus, we found that parvovirus infectivity is unaffected by interferon treatment of human normal or tumor cells. Finally, parvoviral replication was unimpaired by interferon in four human tumor types, including those with residual interferon functionality. We conclude that deficits in the interferon antiviral response of cancer cells do not contribute to parvoviral oncoselectivity in human cells. The interferon-resistant phenotype of parvoviruses may give them an advantage over interferon-sensitive oncolytic viruses in tumors showing residual interferon functionality.

Regulation of type I-interferon responses in the human epidermal melanocyte cell line SKMEL infected by the Ross River alphavirus

“…Of note, melanocytes will induce the expression of IFN-type I (alpha and beta) particularly in response to single stranded RNA like molecules such as poly I:C to mimic viral infection [5]. However, IFN-beta response of melanocytes is 1000 fold lower when compared to that of human astrocytes or fibroblasts virally-infected [6].…”

Induction of an Embryonic Mouse Innate Immune Response following Inoculation In Utero with Minute Virus of Mice

“…Depending on the host and virus combination, infection may provoke an innate immune response (24,26,30) or not (23,27,30,65). Infection may be either blocked by exogenous activation of an innate response (20,21,23,24) or not (26,27,(65)(66)(67). The experimental systems are sometimes close enough in detail that the variance in results is difficult to reconcile.…”

“…In a similar experimental system (26), weak and delayed interferon (IFN) production that was insufficient to induce an antiviral state was observed. In contrast, Paglino and colleagues showed that these viruses fail to stimulate a type I interferon response in normal or transformed human cells (27). Independent studies of two protoparvoviruses, Kilham rat virus (KRV) (28,29) and MVMp (30), provide some evidence for innate immune activation in vitro via Toll-like receptor 9 (TLR9).…”

The immunology and inflammatory responses of human melanocytes in infectious diseases

“…leptospira spirochetes) are known to directly infect human melanocytes and derived cell lines such as SKMEL-28 or MeWo as illustrated in Figure 1. These infections may disturb metabolic functions leading to hypopigmentation (14,15). The mechanisms may be indirect and involving programmed-cell death of the infected melanocytes in an attempt to thwart off the infectious challenge.…”