VMIC 124 Reporting Guidelines PDF

VMIC 124 REPORTING GUIDELINES GUIDELINES 1. Use the following format: I. INTRODUCTION a. ETIOLOGY b. TAXONOMY AND REPRESENTATIVE DISEASES c. CHARACTERISTICS OF THE INFECTIOUS AGENT i. Virion properties ii. Known Receptors and Cell Tropism I...

VMIC 124 REPORTING GUIDELINES GUIDELINES 1. Use the following format: I. INTRODUCTION a. ETIOLOGY b. TAXONOMY AND REPRESENTATIVE DISEASES c. CHARACTERISTICS OF THE INFECTIOUS AGENT i. Virion properties ii. Known Receptors and Cell Tropism II. TRANSMISSION AND IMMUNE RESPONSE a. MAIN MODES OF TRANSMISSION b. METHODS IN EVADING THE IMMUNE SYSTEM III. CLINICAL SIGNS AND SYMPTOMS (OF REPRESENTATIVE DISEASES) a. SYMPTOMS b. PATHOGENESIS IV. DIAGNOSTIC TESTS V. TREATMENT AND CONTROL 2. The presentation should be about twenty five minutes long, with five minutes for Q&A and synthesis. 3. The professor reserves the right to invite an audience to any of the reports as he deems necessary. 4. The report will be graded based on format, content (as a group), and presentation / delivery (individually). EACH member is required to present a section of their report. The breakdown for the scoring is as follows: Format 10 pts. Content 30 pts. Presentation / delivery 10 pts. 5. Presenters are required to upload a.pdf format of their presentations on our Discord server under the channel #vmic-124-notes a day before their online presentation. BONUS: Additional points are given to those who will be dressing up formally during their presentation. Points are given to those who will ask sensible questions during the reporting, or on discord. Points will be awarded to reporters when answering questions correctly during the report or over discord.  I. INTRODUCTION Papovaviruses, historically grouped under the family Papovaviridae, include viruses that are significant in veterinary medicine due to their impact on animal health. These viruses are known for causing various diseases in animals, ranging from benign growths to severe systemic infections. a. Etiology Papovaviruses are responsible for a range of diseases in animals, primarily through their ability to induce cell proliferation and transformation. They can cause benign lesions like warts and more severe conditions such as cancers and systemic infections. Oncogenic viruses are acquired through close contact (including sexual contact), injection, fomites, and unknown means. These viruses infect specific cells in target tissues, becoming persistent and potentially transforming host cells, leading to malignancy. Families with oncogenic viruses include Retroviridae, Hepadnaviridae, Papovaviridae, Adenoviridae, and Herpesviridae. b. Taxonomy and Representative Diseases The family Papovaviridae has been reclassified into two separate families: Papillomaviridae: This family includes viruses that cause papillomas (warts) in various animals. For example, bovine papillomavirus (BPV) causes warts in cattle, which can sometimes progress to cancer. Polyomaviridae: This family includes viruses like avian polyomavirus, which causes Budgerigar Fledgling Disease, a serious condition in young birds. Papovaviruses. DNA, 40 mu to 50 mu, cubic symmetry, ether resistant, non-enveloped. Common wart Bovine papilloma Canine oral papilloma Rabbit oral papilloma Rabbit papilloma Polyoma SV 40 Genital papilloma of swine Pathogens: Genus: Polyomavirus: Mouse polyomavirus  SV40 virus (both of which have been useful models for the study of viral oncogenesis) Budgerigar fledgling disease virus (the only papovavirus that causes an acute disease) Genus: Papillomavirus: Human papillomaviruses (more than 70 types; cause of warts; particular types are associated with cancer of the cervix, anus, and pharynx) Bovine papillomaviruses (cause of cutaneous papillomas in cattle), Canine oral papillomatosis virus Rabbit papillomavirus. Papillomaviruses cause lesions in many other species of mammals and birds. c. Characteristics of the Infectious Agent i. Virion Properties Papovaviruses are small, non-enveloped viruses with icosahedral capsids approximately 45 (genus Poly-omavirus) and 55 (genus Papillomavirus) nm in diameter. The genome consists of a single molecule of circular double-stranded DNA, 5 (genus Polyomavirus) and 8 kbp (genus Papillomavirus) in size. The capsid is composed of 72 capsomeres and encloses a double- stranded DNA genome. Genomic DNA is infectious. Infection often is persistent, with the viral genome carried in an episomal form or integrated into the host cell DNA. These viruses are highly resistant to environmental conditions, including changes in temperature and pH, making them particularly hardy in various environments. Individual polyomaviruses and papillomaviruses have narrow host ranges. ii. Known Receptors and Cell Tropism Papovaviruses exhibit specific cell tropism, meaning they preferentially infect certain cell types. For example: Bovine papillomaviruses (BPVs) primarily infect epithelial cells, leading to the formation of warts and, in some cases, cancers in cattle. Avian polyomaviruses infect a variety of avian species, particularly young birds, causing systemic infections that can be fatal. These viruses often enter cells through specific receptors, although the exact receptors can vary between different types of papovaviruses. For instance, avian polyomavirus is known to infect a wide range of avian cells, leading to widespread systemic disease  II. TRANSMISSION AND IMMUNE RESPONSE a. MAIN MODES OF TRANSMISSION Direct Contact Indirect ( in contact with contaminated equipment like halter, nose lead, grooming, earmarking equipment, post rubbing etc.) b. METHOD IN EVADING THE IMMUNE SYSTEM Expressing viral oncogenes E6 and E7 - The viral immune evasion proteins constitute useful tool to block defined stages of the MHC class 1 presentation pathway, and in this way it avoids the host immune response - The E7 binds to and degrades tumor suppressor Rb(retinoblastoma) and the E6 binds to and inactivates tumor suppressor p53, these proteins E6 and E7 are highly effective at disrupting cell-cycle checkpoints Passive immune evasion strategies - Minimization of antigen production during the vegetative virus life cycle thus minimizing presentation to the host immune system. Modulation of the Pathogen Recognition Receptor(PRR) - The viral oncoproteins block the PRR signal transduction cascade - e.g. Toll-like receptor 9 (TLR9) which recognize double-stranded DNA molecules and trigger downstream inflammatory cascade, the viral oncoproteins suppress TLR9 expression in keratinocytes Inhibition of antiviral molecules - Reduction of MHC I expression affects the cytotoxic T lymphocytes (CTLs) mediated-killing due to the reduced presentation of pathogen-derived peptides by MHC class I molecules on the surface of keratinocytes it can not recognize and kill the pathogen Inhibition of the transcription of genes associated with immune response - The downregulation of NF-κB pathway, as a result of binding of E6 and E7 to coactivators of NF-κB in the nucleus - NF-κB play a key role in immune surveillance by promoting the cellular expression of genes involved in antigen presentation, IFNs, β-defensines, and cytokine production Interference with Langerhans cells (LC) trafficking - Langerhans cells (LCs) are specialized antigen presenting cells found in the epidermis as a part of immune sentinels it also enables the preparation of adaptive immune cells - Interference with LC trafficking in and out of the epidermis can therefore assist in immune evasion (downregulation of CCL20) Ingestion of bracken fern ( Pteridium aquilinum )  - a major contributing factor (both cocarcinogen and immunosuppressive agent) in the transition from benign papillomas to invasive carcinoma of the alimentary tract or bladder, the latter leading to so-called chronic endemic hematuria. Pathogen Recognition Receptor(PRR)- recognize pathogen-associated molecular patterns presented by the virus III. CLINICAL SIGNS AND SYMPTOMS a. PAPILLOMA SYMPTOMS - Cutaneous warts, mucosal warts, squamous cell carcinoma, difficulty breathing and swallowing, lethargy POLYOMA SYMPTOMS - mainly birds, feather loss or damage, lethargy and anorexia, hemorrhage, ☠️ death ☠️. b. PATHOGENESIS PAPILLOMA - develop after an abrasion on the skin is made and the virus interacts with the skin. Infection of the epithelial cells result in hyperplasia with subsequent degeneration and hyperkeratinization. The replication of papillomavirus DNA during normal replication of basal keratinocytes maintains latent. Papillomavirus are dependent on the nuclear machinery of the infected cell for replication. However, once a basal cell loses its ability to divide, degradation of occur. The key property of papillomavirus is their ability to force the infected cell to keep dividing and retain their nuclei via expression of additional E genes. Papilloma viruses have developed ways to allow chronic infection by lowering the host's immune reaction. Symptoms will show about 4 to 6 weeks after exposure. Stages in the pattern of papilloma development can be observed. Stage 1, papillomas appear as slightly raised plaques at about 4 weeks. Stage 2, virus replication and crystalline aggregates of virions in lesion at about 8 weeks. Stage 3, characterized by fibrotic, pedunculated bases and rough, lobate, or fungiform surfaces at about 12 weeks. At about 6 months, papilloma lumps will detached to the skin by necrosis at the base of the infection. A more simpler explanation : virus infection initially occurs in actively dividing basal cells in the stratum basale(deepest layer of the skin). Virus-induced hyperplasia - due to a virus encoded protein - result in increased basal cell division and delayed maturation of cells in stratum spinosum. The cells subsequently undergo degeneration and hyperkeratinization. Virus accumulation most noticeable in stratum granulosum. Virions are shed with exfoliated cells of stratum corneum of the skin. Hyperplasia - increase in tissue size due to increase in number of cells Hyperkeratinization - excessive cells cornification, mag thicken yung skin Squamous cell carcinoma - type of cancer that starts as a growth of cell on the skin  Cell differentiation - process of cell becoming specialized (e.g. stem cell into neurons) PATHOGENESIS ON ANIMALS BOVINE - papillomas and fibropapillomas are more common In cattle than any other domestic animals. All ages can be affected, but incidence is highest in calves and yearlings. Bovine papillomavirus 1, 2, 13, and 14, which are members of Deltapapillomavirus, BPV - 3, 4, 6, 9, 10, 11, and 12 are members of Xipapillomavirus, BPV - 5 and 8 of Epsilonpapillomavirus and BPV-7 which is a member of Dyoxipapillomavirus. Historically, each papillomavirus are thought to be specific papilloma on a specific body location. However, it is now apparent that multiple different papillomavirus types are present in most bovine papillomas making it difficult to determine which of these virus actually caused the papilloma. The virus can transmitted by fomites, including contaminated milking equipment, halters, nose leads, grooming and earmaking equipment, rubbing post and wire fence. Teat and udder papilloma are common in dairy cattle. Infection of epithelial cells result in hyperplasia and hyperkeratinization, usually within 6 weeks of exposure. In general, papillomas persist for 1-6 months before immune mediated regression, multiple warts regress simultaneously. Papilloma cause two different subtype of papilloma in cattle, squamous papilloma and fibropapillomas. Squamous papilloma, caused by BPV - 4, develop in caudal oral cavity, esophagus, and rumen. Fibropapilloma, caused by BPV - 1, 2, and 5, are common on the udder, teats, head, neck, shoulders, but may also occur in upper alimentary tract, vagina, vulva, penis, and anus. Bovine papillomaviruses have also been associated with neoplasia, notably BPV - 2 associated bladder cancer and BPV - 4 associated upper alimentary cancer. Both are highly dependent on the exposure to bracken fern, because of its immunosuppresive and carcinogenic properties EQUINE - Equine papillomavirus cause cutaneous papilloma, aural plaques genital papillomas, and increasingly associated with penile and preputial squamous cell carcinoma. CANINE - Oral papillomas caused by CPV - 1 and possibly CPV - 13 are the most common papillomavirus In dogs. Warts usually first develop on the lips, but can spread to buccal mucosa, tongue, leading to difficulty in swallowing and breathing. POLYOMA - Avian polyomavirus (APV) causes disease in young parrots. There are two forms of the disease based on affected species: budgerigar fledgling disease and non-budgerigar polyoma infection. Both are characterized by peracute to acute death of preweaned neonates. Clinical signs occur 7–10 days after exposure and include lethargy, crop stasis, and death within 24–48 hours. Surviving budgerigars >3 weeks old often exhibit feather dystrophy (French molt or feather dusters). Older nonbudgerigar psittacines may have subclinical disease or hemorrhages and coagulopathies. Adult birds typically are resistant to infection; they will seroconvert and shed the virus for up to 90 days, then clear the infection. Antemortem diagnosis is accomplished with DNA probes of cloacal swab and blood samples. Aviary control methods include not housing budgerigars or lovebirds with other species, strict hygiene, limiting traffic in the nursery, and strict quarantine and testing of new birds. A vaccination is available.The typical presentation of budgerigar fledging disease is a well-fleshed juvenile, just before fledgling age, with acute onset of lethargy, crop stasis, and death within 24–48 hours. Other clinical signs are cutaneous hemorrhage, abdominal distention, and feather abnormalities. Surviving budgerigars >3 weeks old often exhibit feather dystrophy (French molt or feather dusters). In other species of psittacines < 4 months old, the infection is often fatal. Older nonbudgerigar psittacines may have subclinical disease or hemorrhages and coagulopathies IV. DIAGNOSTIC TESTS Diagnostic tests for Papovaviridae (which includes Papillomaviruses and Polyomaviruses) vary depending on the species, clinical presentation, and suspected virus. Here are some common diagnostic approaches: Papillomaviruses (e.g., Bovine Papillomavirus, Canine Papillomavirus): 1. Polymerase Chain Reaction (PCR): Detects viral DNA in tissue samples (e.g., skin lesions, tumors). 2. Histopathology: Examines tissue samples for characteristic lesions. 3. Immunohistochemistry: Detects viral antigens in tissue samples. 4. In-situ hybridization: Localizes viral DNA in tissue samples. 5. Serology: Measures antibodies against specific papillomaviruses. Polyomaviruses (e.g., BK Polyomavirus in monkeys, Mouse Polyomavirus): 1. PCR: Detects viral DNA in urine, blood, or tissue samples. 2. Serology: Measures antibodies against specific polyomaviruses. 3. Viral culture: Isolates the virus from urine or tissue samples. 4. Immunofluorescence: Detects viral antigens in tissue samples. Species-specific diagnostic tests: 1. Bovine Papillomavirus (BPV): - PCR-based tests (e.g., BPV-1, BPV-2) - ELISA (enzyme-linked immunosorbent assay) 2. Canine Papillomavirus (CPV): - PCR-based tests - Immunohistochemistry 3. Equine Papillomavirus (EPV): - PCR-based tests - Serology Sample collection: 1. Tissue biopsies or lesions (papillomaviruses) 2. Urine samples (polyomaviruses) 3. Blood samples (serology) 4. Swab samples (oral, genital, or skin lesions) Interpretation: Positive test results indicate infection or exposure. Negative results do not rule out infection, as viral loads may be low or transient. V. TREATMENT AND CONTROL Papillomaviruses infect a variety of animal species: Cattle (bovine papillomavirus) Horses (equine papillomavirus) Dogs (canine oral papillomavirus)  Cats (feline papillomavirus) Papilloma virus under microscope A. General Treatment a. Surgical Removal - For cutaneous papillomas (warts), surgical excision is often the most effective approach. Ex. Cryotherapy, Laser surgery, or electrosurgery - depending on the size and location. Cryotherapy- involves freezing a wart using a very cold substance (usually liquid nitrogen).  Laser Surgery b. Topical Therapies - chemical treatments (Podophyllin and Imiquimod), may be used to topically to promote wart regression in some species. It stimulate the immune system to attack the viral lesions. Definitions: Topical therapy - refers to skin care chiefly with moisturizers, and to inflammation control chiefly with topical steroids and tacrolimus ointments (immunosuppressive ointment, topical calcineurin inhibitor). Podophyllin - Podophyllin is a cytotoxic material extracted from Podophyllum peltatum and Podophyllum hexandrum and is widely used for the treatment of genital warts. Imiquimod - is a medication used to manage and treat anogenital warts, superficial basal cell carcinomas, and actinic keratoses. c. Immune-Modulation - vaccines or autogenous vaccines (created from the animal’s own viral material) have been used in some species to stimulate the immune system and potentially clear the infection. More common in cattle and in horses. B. Control - this focuses on reducing transmission and managing outbreaks. a. Vaccination - Cattle: to reduce warts that can hide quality and milk production. - Horses: controlling equine sarcoids (tumors caused by BPV) b. Environmental Management: - Reducing exposure to fomites (inanimate objects orrr equipments) as the virus can remain stable in the environment for prolonged periods. c. Isolation Polyomaviridae - less commonly associated with disease in animals compared to papillomaviruses, but they can still cause significant health issue, especially in birds. Polyomaviridae under microscope A. Treatment - no specific treatments but generally focuses on supportive care. a. Supportive care: Avian polyomavirus - fluids, nutritional support and antibiotics to prevent secondary bacterial infections. b. Euthanasia: recommended for severe outbreaks. B. Control a. Vaccination b. Biosecurity measures - Quarantining new birds - Disinfection of cages and equipments - Limiting contact between non-infected and infected birds. c. Monitoring’ - Regular health checks - Screening for the virus Vaccines for Bovine Papillomavirus DNA Vaccines DNA vaccines are able to stimulate effective cytotoxic T lymphocyte and antibody responses by delivering foreign antigens to antigen presenting cells that stimulate CD4+ and CD8+ T cells, and therefore play a very important role in the prevention and control of infectious diseases. Compared to traditional vaccines, naked plasmid DNA vaccines have the following advantages: i) they can be produced in a short time; ii) the cost of large-scale production is considerably lower; iii) commercial sales do not require cold chains due to being stable at room temperature. The E5 protein is one of the major BPV oncoproteins that acts by disrupting the mechanisms of growth inhibition and cell cycle control. In addition, it interacts with growth factor receptors to activate cell proliferation. The L2 protein is a minor viral capsid protein but is essential for papillomavirus infection. It is responsible for binding to the second viral receptor, thereby promoting the exit from the endosome and the delivery of the viral genome to the nucleus. For these reasons, BPV E5 and L2 proteins are considered to be strong candidates for DNA vaccines against bovine papillomatosis. Virus-like Particles (VLPs) Vaccines Virus-like particles (VLPs) or chimeric VLPs (CVLPs) exhibit morphological and immunological characteristics of natural virions, but are not infectious and do not cause disease due to the absence of a genome. The major capsid proteins of the virus, including L1 and L2, initially self - assemble into multimer, which can, in turn, unite to form higher-order structures (VLPs). Currently, VLPs or CVLPs of various types of BPV have been produced from baculovirus-insect, yeast, and plant expression systems in Creative Biolabs. These VLPs are highly immunogenic and have been shown confer protection against future infection by BPV types from which they were derived. Consequently, they have utility as a potential prophylactic vaccine against BPV. References: Bovine Papillomavirus - an overview | ScienceDirect Topics. (n.d.). Www.sciencedirect.com. https://www.sciencedirect.com/topics/veterinary-science-and-veterinary-medicine/bovine- papillomavirus Nigel James Maclachlan, Dubovi, E. J., & Fenner, F. (2011). Fenner’s veterinary virology. Elsevier Academic Press. Murphy, F. A. (1999). Veterinary virology, 3rd Edition. Academic. Giuseppe Borzacchiello, Franco Roperto. Bovine papillomaviruses, papillomas and cancer in cattle. Veterinary Research, 2008, 39 (5), pp.1. 10.1051/vetres:2008022. hal-00902936 Viral diseases of pet birds - viral diseases of pet birds (no date) MSD Veterinary Manual. https://www.msdvetmanual.com/exotic-and-laboratory-animals/pet-birds/viral-diseases-of-pet- birds (Accessed: 17 September 2021).