Newcastle disease

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Avian avulavirus 1
CSIRO ScienceImage 325 The Poultry Killing Newcastle Disease.jpg
Avian avulavirus 1 (stained in brown) in the conjunctiva of a chicken
Virus classification Red Pencil Icon.png
(unranked): Virus
Phylum: Negarnaviricota
Class: Monjiviricetes
Order: Mononegavirales
Family: Paramyxoviridae
Genus: Avulavirus
Species:
Avian avulavirus 1

Newcastle disease is a contagious viral bird disease affecting many domestic and wild avian species; it is transmissible to humans. [1] It was first identified in Java, Indonesia, in 1926, and in 1927, in Newcastle-upon-Tyne, England (whence it got its name). However, it may have been prevalent as early as 1898, when a disease wiped out all the domestic fowl in northwest Scotland. [2] Its effects are most notable in domestic poultry due to their high susceptibility and the potential for severe impacts of an epizootic on the poultry industries. It is endemic to many countries.

Bird Warm-blooded, egg-laying vertebrates with wings, feathers and beaks

Birds, also known as Aves, are a group of endothermic vertebrates, characterised by feathers, toothless beaked jaws, the laying of hard-shelled eggs, a high metabolic rate, a four-chambered heart, and a strong yet lightweight skeleton. Birds live worldwide and range in size from the 5 cm (2 in) bee hummingbird to the 2.75 m (9 ft) ostrich. They rank as the world's most numerically-successful class of tetrapods, with approximately ten thousand living species, more than half of these being passerines, sometimes known as perching birds. Birds have wings which are more or less developed depending on the species; the only known groups without wings are the extinct moa and elephant birds. Wings, which evolved from forelimbs, gave birds the ability to fly, although further evolution has led to the loss of flight in flightless birds, including ratites, penguins, and diverse endemic island species of birds. The digestive and respiratory systems of birds are also uniquely adapted for flight. Some bird species of aquatic environments, particularly seabirds and some waterbirds, have further evolved for swimming.

Disease abnormal condition negatively affecting organisms

A disease is a particular abnormal condition that negatively affects the structure or function of part or all of an organism, and that is not due to any external injury. Diseases are often construed as medical conditions that are associated with specific symptoms and signs. A disease may be caused by external factors such as pathogens or by internal dysfunctions. For example, internal dysfunctions of the immune system can produce a variety of different diseases, including various forms of immunodeficiency, hypersensitivity, allergies and autoimmune disorders.

Zoonosis infectious disease that is transmitted between species (sometimes by a vector) from animals other than humans to humans or from humans to other animals

Zoonoses are infectious diseases caused by bacteria, viruses and parasites that spread between animals and humans.

Contents

Exposure of humans to infected birds (for example in poultry processing plants) can cause mild conjunctivitis and influenza-like symptoms, but the Newcastle disease virus (NDV) otherwise poses no hazard to human health. Interest in the use of NDV as an anticancer agent has arisen from the ability of NDV to selectively kill human tumour cells with limited toxicity to normal cells.

Conjunctivitis inflammation of the outermost layer of the eye and the inner surface of the eyelids

Conjunctivitis, also known as pink eye, is inflammation of the outermost layer of the white part of the eye and the inner surface of the eyelid. It makes the eye appear pink or reddish. Pain, burning, scratchiness, or itchiness may occur. The affected eye may have increased tears or be "stuck shut" in the morning. Swelling of the white part of the eye may also occur. Itching is more common in cases due to allergies. Conjunctivitis can affect one or both eyes.

Influenza infectious disease

Influenza, commonly known as the flu, is an infectious disease caused by an influenza virus. Symptoms can be mild to severe. The most common symptoms include: high fever, runny nose, sore throat, muscle pains, headache, coughing, sneezing, and feeling tired. These symptoms typically begin two days after exposure to the virus and most last less than a week. The cough, however, may last for more than two weeks. In children, there may be diarrhea and vomiting, but these are not common in adults. Diarrhea and vomiting occur more commonly in gastroenteritis, which is an unrelated disease and sometimes inaccurately referred to as "stomach flu" or the "24-hour flu". Complications of influenza may include viral pneumonia, secondary bacterial pneumonia, sinus infections, and worsening of previous health problems such as asthma or heart failure.

No treatment for NDV is known, but the use of prophylactic vaccines [3] and sanitary measures reduces the likelihood of outbreaks.

Causal agent

The causal agent, Newcastle disease virus (NDV), is a variant of avian paramyxovirus 1 (APMV-1), a negative-sense, single-stranded RNA virus. NDV/APMV-1 belong to the genus Avulavirus in the family Paramyxoviridae . Transmission occurs by exposure to faecal and other excretions from infected birds, and through contact with contaminated food, water, equipment, and clothing.

RNA family of large biological molecules

Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and DNA are nucleic acids, and, along with lipids, proteins and carbohydrates, constitute the four major macromolecules essential for all known forms of life. Like DNA, RNA is assembled as a chain of nucleotides, but unlike DNA it is more often found in nature as a single-strand folded onto itself, rather than a paired double-strand. Cellular organisms use messenger RNA (mRNA) to convey genetic information that directs synthesis of specific proteins. Many viruses encode their genetic information using an RNA genome.

Virus Type of non-cellular infectious agent

A virus is a small infectious agent that replicates only inside the living cells of an organism. Viruses can infect all types of life forms, from animals and plants to microorganisms, including bacteria and archaea.

A genus is a taxonomic rank used in the biological classification of living and fossil organisms, as well as viruses, in biology. In the hierarchy of biological classification, genus comes above species and below family. In binomial nomenclature, the genus name forms the first part of the binomial species name for each species within the genus.

Strains

NDV strains can be categorised as velogenic (highly virulent), mesogenic (intermediate virulence), or lentogenic (nonvirulent). Velogenic strains produce severe nervous and respiratory signs, spread rapidly, and cause up to 90% mortality. Mesogenic strains cause coughing, affect egg quality and production, and result in up to 10% mortality. Lentogenic strains produce mild signs with negligible mortality.

Virulence is a pathogen's or microbe's ability to infect or damage a host.

Use as an anticancer agent

In 1999, promising results were reported using an attenuated strain of the Newcastle virus, code named MTH-68, in cancer patients [4] by researchers who had isolated the strain in 1968. [5] [6] It appears the virus preferentially targets and replicates in certain types of tumor cells, leaving normal cells almost unaffected. In 2006, researchers from the Hebrew University also succeeded in isolating a variant of the NDV, code named NDV-HUJ, which showed promising results in 14 glioblastoma multiforme patients. [7] In 2011, Memorial Sloan–Kettering Cancer Center researchers found that NDV modified with the viral protein NS1 had a higher specificity for cancer cells that overexpressed the antiapoptotic factor Bcl-xL. The researchers suggested in cells that resist the normal inducement of apoptosis when infected will give NDV more time to incubate in cell and spread. Many cancer cells will overexpress antiapoptotic factors as part of tumor development. This mechanism of delaying apoptosis in abnormal cells gives NDV the specificity it needs to be an efficient cancer-fighting oncolytic virus. [8]

History of NDV in cancer therapy

Though the oncolytic effect of NDV was documented already in the 1950s, the main advances of viruses in cancer therapy came with the advent of reverse genetics technologies [9] [10] With these new possibilities, studies of modified NDV strains with enhanced cancer-treatment properties have been put on the agenda. A study [10] demonstrated the engineered Hitcher B1 NDV/F3aa strain could be modified to express a highly fusogenic F-protein in combination with immunostimulatory molecules such as IFN-gamma, interleukin 2, or tumor necrosis factor alpha. Promising results were discovered with proteins associated to the adaptive immune system, which paved the way for possibilities to use NDV to create a tumor-associated antigen. Another study showed how NDV/F3aa could be modified to express NS1, an influenza virus protein with capability to modulate with the innate immune response, for example, by suppressing the induction of the cellular interferons. [11]

NDV pros and cons in cancer therapy

NDV possesses many unique anticancer properties and thereby provides an excellent base in virotherapy research. NDV has selectivity on oncogenic cells, where it replicates without, or in a less pronounced way, harming normal cells. [12] [13] It binds, fuses into and replicates within the infected cells’ cytoplasm independent of cell proliferation. [12] One of the main issues using NDV treatment is the host/patient immune response against the virus itself, which prior to the time of the reverse genetics technology, decreased the applicability of NDV as a cancer treatment. [9] Kuruppu & Tanabe 2005) [14]

NDV-induced mechanisms leading to tumor cell death

The precise way in which the presence of NDV induces tumor cell death remains to be clarified and may show variation regarding the strains of NDV used and which type of cancer is targeted. NDV triggers apoptosis [12] in a wide range of cancer cell types via the mitochondrial/intrinsic pathway, through loss of membrane potential and thereby inducing release of cytochrome c in the tumor cell. The results [12] also indicate the extrinsic pathway is activated by TNF-related, apoptosis-inducing ligand-induced, NDV-mediated apoptosis in a late stage. Another study [15] found a hyperfusogenic NDV/F3aa(L289A) with refined abilities to fuse into somatic cells. NDV has aggregating properties causing syncytia formations of tumor cells, which, apart from amplifying immune-based cell killing, also results in necrosis of cells. This pathway was believed to lead to a considerable boost of immune activation and potentially an antitumor response, which was supported by observations of a significant accumulation of NK-cells and neutrophils following the infusion of NDV/F3aa(L289A) in hepatocellular carcinoma cells. In addition, an increase of CD4+ and CD8+ T-cells occurs within the tumor cells when inducing NDV/F3aa recombined with the cytokine interleukin-2 (IL-2). [16] An NDV/F3aa-IL-2 strain induced the immune system, giving a cytotoxic effect on the tumor cells. [17] A 15-year study on patients with malignant melanoma showed increased numbers of oligoclonal CD8+ T-cells in the blood, suggesting vaccination with NDV oncolysates was associated with prolonged survival among the patients, and CD8+ T-cells played an important role. [18]

Transmission

NDV is spread primarily through direct contact between healthy birds and the bodily discharges of infected birds. The disease is transmitted through infected birds' droppings and secretions from the nose, mouth, and eyes. NDV spreads rapidly among birds kept in confinement, such as commercially raised chickens.

High concentrations of the NDV are found in birds' bodily discharges; therefore, the disease can be spread easily by mechanical means. Virus-bearing material can be picked up on shoes and clothing and carried from an infected flock to a healthy one.

NDV can survive for several weeks in a warm and humid environment on birds' feathers, manure, and other materials. It can survive indefinitely in frozen material. However, the virus is destroyed rapidly by dehydration and by the ultraviolet rays in sunlight. Smuggled pet birds, especially Amazon parrots from Latin America, pose a great risk of introducing NDV into the US. Amazon parrots are carriers of the disease, but do not show symptoms, and are capable of shedding NDV for more than 400 days.

Clinical findings

Clinical signs

Egg drop after a (otherwise asymptomatic) Newcastle disease infection in a duly vaccinated broiler parent flock Ponaedje fasse pesse.jpg
Egg drop after a (otherwise asymptomatic) Newcastle disease infection in a duly vaccinated broiler parent flock

Signs of infection with NDV vary greatly depending on factors such as the strain of virus and the health, age and species of the host.

The incubation period for the disease ranges from 4 to 6 days. An infected bird may exhibit several signs, including respiratory signs (gasping, coughing), nervous signs (depression, inappetence, muscular tremors, drooping wings, twisting of head and neck, circling, complete paralysis), swelling of the tissues around the eyes and neck, greenish, watery diarrhea, misshapen, rough- or thin-shelled eggs and reduced egg production.

In acute cases, the death is very sudden, and, in the beginning of the outbreak, the remaining birds do not seem to be sick. In flocks with good immunity, however, the signs (respiratory and digestive) are mild and progressive, and are followed after 7 days by nervous symptoms, especially twisted heads.

Postmortem lesions

Petechiae in the proventriculus and on the submucosae of the gizzard are typical; also, severe enteritis of the duodenum occurs. The lesions are scarce in hyperacute cases (first day of outbreak).

Diagnosis

Immunological tests

Enzyme-linked immunosorbent assay, polymerase chain reaction, and sequence technology tests have been developed.

Virus isolation

Samples

For routine isolation of NDV from chickens, turkeys, and other birds, samples are obtained by swabbing the trachea and the cloaca. Cotton swabs can be used. The virus can also be isolated from the lungs, brain, spleen, liver, and kidneys.

Handling

Prior to shipping, samples should be stored at 4°C (refrigerator). Samples must be shipped in a padded envelope or box. Samples may be sent by regular mail, but overnight is recommended. [19]

Prevention

Any animals showing symptoms of Newcastle disease should be isolated immediately. New birds should also be vaccinated before being introduced to a flock. An inactivated viral vaccine is available, as well as various combination vaccines. [3] [20] [21] A thermotolerant vaccine is available for controlling Newcastle disease in underdeveloped countries. [22]

Related Research Articles

A cancer vaccine is a vaccine, that either treats existing cancer or prevents development of a cancer. Vaccines that treat existing cancer are known as therapeutic cancer vaccines.

An oncovirus is a virus that can cause cancer. This term originated from studies of acutely transforming retroviruses in the 1950–60s, often called oncornaviruses to denote their RNA virus origin. It now refers to any virus with a DNA or RNA genome causing cancer and is synonymous with "tumor virus" or "cancer virus". The vast majority of human and animal viruses do not cause cancer, probably because of longstanding co-evolution between the virus and its host. Oncoviruses have been important not only in epidemiology, but also in investigations of cell cycle control mechanisms such as the retinoblastoma protein.

Cancer immunotherapy The artificial stimulation of the immune system to treat cancer, improving on the systems natural ability to fight cancer

Cancer immunotherapy is the artificial stimulation of the immune system to treat cancer, improving on the system's natural ability to fight cancer. It is an application of the fundamental research of cancer immunology and a growing subspecialty of oncology. It exploits the fact that cancer cells often have tumor antigens, molecules on their surface that can be detected by the antibody proteins of the immune system, binding to them. The tumor antigens are often proteins or other macromolecules. Normal antibodies bind to external pathogens, but the modified immunotherapy antibodies bind to the tumor antigens marking and identifying the cancer cells for the immune system to inhibit or kill.

An oncolytic virus is a virus that preferentially infects and kills cancer cells. As the infected cancer cells are destroyed by oncolysis, they release new infectious virus particles or virions to help destroy the remaining tumour. Oncolytic viruses are thought not only to cause direct destruction of the tumour cells, but also to stimulate host anti-tumour immune system responses.

Virotherapy is a treatment using biotechnology to convert viruses into therapeutic agents by reprogramming viruses to treat diseases. There are three main branches of virotherapy: anti-cancer oncolytic viruses, viral vectors for gene therapy and viral immunotherapy. These branches utilize three different types of treatment methods: gene overexpression, gene knockout, and suicide gene delivery. Gene overexpression adds genetic sequences that compensate for low to zero levels of needed gene expression. Gene knockout utilizes RNA methods to silence or reduce expression of disease-causing genes. Suicide gene delivery introduces genetic sequences that induce an apoptotic response in cells, usually to kill cancerous growths. In a slightly different context, virotherapy can also refer more broadly to the use of viruses to treat certain medical conditions by killing pathogens.

Marek's disease is a highly contagious viral neoplastic disease in chickens. It is named after József Marek, a Hungarian veterinarian. Marek's disease is caused by an alphaherpesvirus known as 'Marek's disease virus' (MDV) or Gallid alphaherpesvirus 2 (GaHV-2). The disease is characterized by the presence of T cell lymphoma as well as infiltration of nerves and organs by lymphocytes. Viruses related to MDV appear to be benign and can be used as vaccine strains to prevent Marek's disease. For example, the related Herpesvirus of Turkeys (HVT), causes no apparent disease in turkeys and continues to be used as a vaccine strain for prevention of Marek's disease. Birds infected with GaHV-2 can be carriers and shedders of the virus for life. Newborn chicks are protected by maternal antibodies for a few weeks. After infection, microscopic lesions are present after one to two weeks, and gross lesions are present after three to four weeks. The virus is spread in dander from feather follicles and transmitted by inhalation.

Viral vectors are tools commonly used by molecular biologists to deliver genetic material into cells. This process can be performed inside a living organism or in cell culture. Viruses have evolved specialized molecular mechanisms to efficiently transport their genomes inside the cells they infect. Delivery of genes, or other genetic material, by a vector is termed transduction and the infected cells are described as transduced. Molecular biologists first harnessed this machinery in the 1970s. Paul Berg used a modified SV40 virus containing DNA from the bacteriophage λ to infect monkey kidney cells maintained in culture.

A panzootic is an epizootic that spreads across a large region, or even worldwide. The equivalent in human populations is called a pandemic.

Genetically modified virus

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Oncolytic herpes virus

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References

  1. ↑ Nelson, CB; Pomeroy, BS; Schrall, K; Park, WE; Lindeman, RJ (Jun 1952). "An outbreak of conjunctivitis due to Newcastle disease virus (NDV) occurring in poultry workers". American Journal of Public Health and the Nation's Health. 42 (6): 672–8. doi:10.2105/ajph.42.6.672. PMC   1526237 . PMID   14924001.
  2. ↑ Macpherson, LW (May 1956). "Some Observations On The Epizootiology Of NewCastle Disease". Canadian Journal of Comparative Medicine and Veterinary Science. 20 (5): 155–68. PMC   1614269 . PMID   17648892.
  3. 1 2 FAO Manual on Vaccines
  4. ↑ Csatary, LK; Moss, RW; Beuth, J; Töröcsik, B; Szeberenyi, J; Bakacs, T (Jan–Feb 1999). "Beneficial treatment of patients with advanced cancer using a Newcastle disease virus vaccine (MTH-68/H)". Anticancer Research. 19 (1B): 635–8. PMID   10216468.
  5. ↑ Csatary, LK; Csatary, E; Moss, RW (Mar 15, 2000). "Re: Scientific interest in Newcastle disease virus is reviving". Journal of the National Cancer Institute. 92 (6): 493–4. doi:10.1093/jnci/92.6.493. PMID   10716968.
  6. ↑ Csatary, LK (October 1971). "Viruses in the treatment of cancer". Lancet. 2 (7728): 825. doi:10.1016/s0140-6736(71)92788-7. PMID   4106650.
  7. ↑ Viruses: The new cancer hunters. isracast.com. 1 March 2006
  8. ↑ Mansour, M.; Palese, P.; Zamarin, D. (2011). "Oncolytic Specificity of Newcastle Disease Virus Is Mediated by Selectivity for Apoptosis-Resistant Cells". Journal of Virology. 85 (12): 6013–23. doi:10.1128/JVI.01537-10. PMC   3126310 . PMID   21471241.
  9. 1 2 Mullen, JT; Tanabe, KK (2002). "Viral oncolysis". The Oncologist. 7 (2): 106–19. doi:10.1634/theoncologist.7-2-106. PMID   11961194.(Flanagan et al. 1955 in Mullen & Tanabe 2002
  10. 1 2 Vigil, A; Park, MS; Martinez, O; Chua, MA; Xiao, S; Cros, JF; Martínez-Sobrido, L; Woo, SL; García-Sastre, A (Sep 1, 2007). "Use of reverse genetics to enhance the oncolytic properties of Newcastle disease virus". Cancer Research. 67 (17): 8285–92. doi:10.1158/0008-5472.CAN-07-1025. PMID   17804743.
  11. ↑ Zamarin, D; Martínez-Sobrido, L; Kelly, K; Mansour, M; Sheng, G; Vigil, A; García-Sastre, A; Palese, P; Fong, Y (Apr 2009). "Enhancement of oncolytic properties of recombinant newcastle disease virus through antagonism of cellular innate immune responses". Molecular Therapy. 17 (4): 697–706. doi:10.1038/mt.2008.286. PMC   2835121 . PMID   19209145.
  12. 1 2 3 4 Elankumaran, S; Rockemann, D; Samal, SK (Aug 2006). "Newcastle disease virus exerts oncolysis by both intrinsic and extrinsic caspase-dependent pathways of cell death". Journal of Virology. 80 (15): 7522–34. doi:10.1128/JVI.00241-06. PMC   1563725 . PMID   16840332.
  13. ↑ Fábián, Z; Csatary, CM; Szeberényi, J; Csatary, LK (Mar 2007). "p53-independent endoplasmic reticulum stress-mediated cytotoxicity of a Newcastle disease virus strain in tumor cell lines". Journal of Virology. 81 (6): 2817–30. doi:10.1128/JVI.02490-06. PMC   1865991 . PMID   17215292.
  14. ↑ Kuruppu, D; Tanabe, KK (May 2005). "Viral oncolysis by herpes simplex virus and other viruses". Cancer Biology & Therapy. 4 (5): 524–31. doi:10.4161/cbt.4.5.1820. PMID   15917655.
  15. ↑ Altomonte, J; Marozin, S; Schmid, RM; Ebert, O (Feb 2010). "Engineered newcastle disease virus as an improved oncolytic agent against hepatocellular carcinoma". Molecular Therapy. 18 (2): 275–84. doi:10.1038/mt.2009.231. PMC   2839313 . PMID   19809404.
  16. ↑ Vigil, A; Martinez, O; Chua, MA; García-Sastre, A (Nov 2008). "Recombinant Newcastle disease virus as a vaccine vector for cancer therapy". Molecular Therapy. 16 (11): 1883–90. doi:10.1038/mt.2008.181. PMC   2878970 . PMID   18714310.
  17. ↑ Zamarin, D; Vigil, A; Kelly, K; García-Sastre, A; Fong, Y (Jun 2009). "Genetically engineered Newcastle disease virus for malignant melanoma therapy". Gene Therapy. 16 (6): 796–804. doi:10.1038/gt.2009.14. PMC   2882235 . PMID   19242529.
  18. ↑ Batliwalla, FM; Bateman, BA; Serrano, D; Murray, D; Macphail, S; Maino, VC; Ansel, JC; Gregersen, PK; Armstrong, CA (Dec 1998). "A 15-year follow-up of AJCC stage III malignant melanoma patients treated postsurgically with Newcastle disease virus (NDV) oncolysate and determination of alterations in the CD8 T cell repertoire". Molecular Medicine (Cambridge, Massachusetts). 4 (12): 783–94. PMC   2230393 . PMID   9990864.
  19. ↑ Newcastle Disease Virus (NDV). avianbiotech.com
  20. ↑ Newcastle Disease Vaccine, B1 Type, B1 Strain, Live Virus. drugs.com
  21. ↑ Merck/Intervet Vaccine
  22. ↑ Robyn Alders; Spradbrow, Peter (2001). Controlling Newcastle disease in village chickens : a field manual. Canberra: ACIAR. ISBN   978-1863203074.
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