Information presented in this section about the use of Newcastle disease virus (NDV) in the treatment of human cancer is summarized in a table located at the end of the section.
NDV is a paramyxovirus that causes Newcastle disease in a wide variety of birds (most notably, in chickens). Reviewed in [1,2,3] This often fatal disease is characterized by inflammation of respiratory tract and of either the brain or the gastrointestinal tract. Reviewed in [1,2,4,5] NDV can also infect humans, but, in humans, it is generally not very virulent, causing only mild flu-like symptoms or conjunctivitis and/or laryngitis. Reviewed in [1,6,7,8,9,10,11,12,13,14] The perception that NDV can replicate up to 10,000 times better in human cancer cells than in most normal human cells [12,15,16,17,18,19] Reviewed in [2,6,7,8,9,10,13,20,21,22,23] has prompted much interest in this virus as a potential anticancer agent. This phenomenon is apparently caused by defects in intracellular antiviral defenses of some cancer cells.[24,25,26] NDV was historically considered a CAM approach, but in recent years it has been extensively studied by the conventional medical community. Also, genetically engineered NDV strains are being developed and studied for their anticancer activity.
The genetic material of NDV is RNA rather than DNA. Reviewed in [1,3,13,18,23,28,29,30,31] As with other types of viruses, essentially all of NDV's replication cycle takes place inside infected cells, which are also known as host cells. Reviewed in [13,18,30,32] During a replication cycle, new virus proteins and copies of the NDV genetic material (i.e., genome) are made in the host cell's cytoplasm. NDV is also an enveloped virus, which means that progeny virus particles are released from infected cells by budding off from them. Reviewed in [18,30,33] In this process, single copies of the NDV genome become wrapped in an outer coat (i.e., an envelope) that is made from a small piece of the host cell's plasma membrane. Generally, the NDV outer coat contains only virus proteins that have been specifically inserted into the host cell's plasma membrane; Reviewed in [18,28,32,33] however, some host cell proteins may be included as well. Reviewed in [34,35] Two specific virus proteins, hemagglutinin-neuraminidase and the fusion protein, are the main NDV proteins found in the outer coat of isolated virus particles. Reviewed in [3,18,28,30]
There are many different strains of NDV, and they have been classified as either lytic or nonlytic for human cells. Lytic strains and nonlytic strains both appear to replicate much more efficiently in human cancer cells than they do in most normal human cells,[12,15,16,17,18,19,20] Reviewed in [13,36] and viruses of both strain types have been investigated as potential anticancer agents. One major difference between lytic strains and nonlytic strains is that lytic strains are able to make infectious progeny virus particles in human cells, whereas nonlytic strains are not. Reviewed in [13,18,28,29,30,37] This difference is due to the ability of lytic strains to produce activated hemagglutinin-neuraminidase and fusion protein molecules in the outer coat of progeny viruses in human cells. The progeny virus particles made by nonlytic strains contain inactive versions of these molecules. Activated hemagglutinin-neuraminidase and fusion protein molecules are required for NDV to enter a cell to replicate. Initial binding of NDV to a host cell takes place through the interaction of hemagglutinin-neuraminidase molecules in the virus coat with sialic-acid-containing molecules (i.e., gangliosides) on the surface of the cell. It is important to note, however, that nonlytic strains of NDV can make infectious progeny viruses in some types of nonhuman cells (e.g., chicken embryo cells), Reviewed in [13,18,28,29,36] thereby allowing these strains to be maintained.