Poxviruses (VetMed 5400) Lecture Notes PDF

Poxviruses Block IV, VetMed 5400 Gary Whittaker, PhD [email protected] 12/5/2024  Outline Introduction to the Poxviruses. – Structure, replication, pathogenesis and properties – 2 subfamilies (28 genera, 96 species)...

Poxviruses Block IV, VetMed 5400 Gary Whittaker, PhD [email protected] 12/5/2024  Outline Introduction to the Poxviruses. – Structure, replication, pathogenesis and properties – 2 subfamilies (28 genera, 96 species) Poxviruses of veterinary importance. – General features, pathogenesis, clinical signs, diagnosis, treatment and control (i) poxviruses in cats (v) poxviruses in other species – Cowpox virus – Orf virus (sheep/goats) (ii) poxviruses in swine – Myxoma virus (rabbits) – Swinepox virus – Ectromelia virus (mice) (iii) poxviruses in poultry – Sheep- and goatpox virus – Fowlpox virus – Lumpy skin disease (cattle) (iv) poxviruses in cattle – Pseudocowpox virus  Learning Objectives 1. Understand the morphological features and infectious cycle in comparison to other DNA (and RNA) viruses 2. Compare the pathogenesis of poxviruses and their disease signs in different animal species *Note: Learning objectives generally describe the minimum knowledge needed to pass the course.  Poxviruses: structure Virion properties: large double stranded DNA (genome: 130- 375 Kbp) surrounded by a core membrane and 2 lateral bodies (replication enzymes). One or two (envelope) lipid membranes Oval, brick shaped, or pleomorphic Host range: can infect both vertebrate and invertebrate animals. Some are zoonotic, but most are very species-specific 220-450 nm long and 140-260 nm wide  Poxviruses: replication Replication in cytoplasm (exception for DNA virus) è cytoplasmic inclusion bodies From Flint Principles of Virology  Poxviruses: pathogenesis Variety of infection routes > through the skin by mechanical means > via the respiratory tract > by the oral route Acute infections (so no latent, persistent, or chronic infections) Local (skin lesions) or systemic (often fatal) depending on entry route  Poxviruses: properties Very old (pharaoh Ramses V died of smallpox in ~1000 BC) WHO new public health Large genomes: concern - used as vectors for gene therapy or recombinant vaccines (rabies in with MPOX wildlife, canarypox) - a variety of immune evasion strategies Smallpox is eradicated, (vaccine), but concern for bioterrorism/synthetic viruses  Poxviruses: properties Successful eradication of smallpox was possible for 4 reasons: 1) There is no other reservoir for smallpox but man (so no animal reservoir) 2) Variola virus (VV) causes only acute infections (so no long-term carrier state: Herpes) 3) WHO created a coordinated vaccination program (no patent, so cheap vaccine, was also very effective); “bifurcated” needle 4) Easy surveillance of the disease: rash localization (varicella zoster virus (VZV): chickenpox/shingles)  Poxviruses: 2 subfamilies fowlpox, canarypox, turkeypox,… sheeppox virus, goatpox, lumpy skin disease myxoma virus, squirrel fibroma, hare fibroma molluscum contagiosum virus vaccinia, variola (smallpox), cowpox*, ectromelia, orf virus*, pseudocowpox* swinepox * zoonosis  Take home #1 Large DNA viruses (use as recombinant vaccines) Replicate exclusively in the cytoplasm of cells Masters in viral immune evasion Very species-specific, some are zoonotic Cause acute infections (no persistence) Variety of infection routes Local (skin) or systemic (fatal) disease  Cowpox General features: Genus Orthopoxvirus Same genus as vaccinia virus and variola virus (smallpox) Its close resemblance to the mild form of smallpox inspired the first smallpox vaccine in humans Used to be common, now rare. Only in Western Europe Causes mild lesion on the udder and teats of dairy cows (papules or ulcerated areas that form scabs) Differential diagnosis: bovine mammillitis (BHV-2) Zoonosis!  Cowpox Cowpox infections in cats: Cats in Eurasia probably get it from rodents (virus reservoir) A single lesion progresses to a general skin rash Erythematous macules develop into vesicles that ulcerate and from scabs (“crusty” lesions) Recovery in 6-8 weeks, although animals with concurrent bacterial or FeLV infections (immunosuppressive) may not survive, often dying of pneumonia Cheetahs rarely survive and almost always die of pneumonia  Cowpox Cowpox infections in people: In Eurasia Cats are most common source for people Localized lesions on the skin Possible generalized malaise, fever, and local lymphadenopathy Most severe in children, many of whom become hospitalized  Swinepox General features: Genus Suipoxvirus Transmitted by either direct contact with lesions or the pig louse (Hematopinus suis) Worldwide, but low incidence (USA: Midwest) Most frequently in young piglets Papules and pustules on the face, ears, inside the legs, and abdomen è dry out è dark scabs (piglets with “spotted” appearance) è heals without scarring Control: eradicate the pig louse  Fowlpox General features: Worldwide disease of poultry caused by a variety of poxviruses that are all antigenically similar (same genus of Avipoxvirus) but are distinct species (eg turkeypox, canarypox, pigeonpox,…) Common disease in backyard chickens that have not been vaccinated 2 disease forms: (i) cutaneous form: proliferative skin lesions, thick scabs (ii) diphtheritic form: diphtheritic membranes in upper respiratory (and/or gastro-intestinal) tract  Fowlpox Pathogenesis & clinical signs: (i) cutaneous form: Infection via biting insects (especially mosquitoes) and wound contamination è skin lesions on beak, comb and wattles è recovery within a few weeks (ii) diphtheritic form: Infection via inhalation è diphtheritic membranes in pharynx, trachea (sloughed necrotic material forms a pseudo-membranes) è open mouth breathing, gasping, coughing, and asphyxiation è anorexia and depression è often fatal  Fowlpox Diagnosis: Clinical signs Virus isolation EM Histology: Bollinger bodies in cytoplasm From Silva et al, Rev. Bras. Cienc. Avic., 2006 Differential diagnosis: infectious laryngotracheitis (ILTV) caused by GHV-1 (Pox: cytoplasmic inclusions, compare with Herpes: intranuclear inclusions!).  Fowlpox Treatment and Control: Management of the mosquito population Vaccination chickens: usually pigeonpox virus, via wing web method or in ovo Recombinant fowlpox vaccine (combined with GHV-1) Long-lasting immunity after recovery from natural infection  Pseudocowpox General features: Genus Parapoxvirus Causative agent of bovine papular stomatitis Most infections go entirely unnoticed. But important for differential diagnosis with foot and mouth disease (but no foot lesions with bovine papular stomatitis) In cattle < 2 years of age: small erosion lesions located on the margins of the lips, muzzle, and buccal mucosa, that heal in a couple of weeks Adult cows: teat lesions Frequent reinfections because of short duration of immunity Zoonosis (farmyard pox. Especially milkers è hand lesions)  Pseudocowpox Clinical signs: farmyard pox:  Orf virus General features: Genus Parapoxvirus Also known as ecthyma contagiosum (or ovine range fever, thistle disease or scabby mouth) Affects primarily the lips of young animals Usually more severe in goats than in sheep The virus is highly resistant in the environment, especially in dried crusts (several years) Differential diagnosis: sheeppox and goatpox (genus capripox) and ulcerative dermatosis (related parapox, but older animals) Zoonosis!  Orf virus Pathogenesis and Clinical signs: Spread via direct contact and fomites. In some environments infection is initiated by scratches from thistles Papules and pustules on the lips and muzzle of young lambs. Followed by encrusting and formation of scabs that will heal without scarring Dr. Philip Scott Dr. Daisy Maher Class of 2020  Orf virus Diagnosis, treatment and control: Clinical signs Direct demonstration of virus in scab material by EM, PCR Prevention of secondary bacterial infections of skin lesions Vaccination: life vaccines è small amount of the live vaccine is brushed over light scarifications of the skin, usually on the inside of the thigh or behind the elbow è careful for transmitting virus to unvaccinated animals (wait until scabs have healed after vaccination)  Myxoma virus General features: Genus Leporipox Spread via direct contact or biting insects (fleas, mosquitoes) Disease outcome depends on the rabbit breed: (ii) only a mild cutaneous fibroma in its natural wild hosts: Argentinian, Mexican, and Californian rabbit (i) a serious, life-threatening, systemic viral disease (myxomatosis) in its aberrant host, the European rabbit Reportable disease [The first poxvirus identified (1898), 22 years before the first human poxviruses were recognized! ]  Myxoma virus General features: Has been introduced in several countries in an attempt to control the rabbit population (Australia, New Zealand) In endemic areas: vaccination of pet rabbits because of insect transmission risk. Pet rabbits are highly susceptible! Hares rarely ever show clinical signs, but can carry the fleas  Myxoma virus Pathogenesis: Primary infection in skin è replication in dermis (mild, primary skin lesions) è infection Langerhans cells that migrate to draining lymph nodes (primary ‘viremia’) è infection T-cells è spread via blood and lymph to liver, spleen, other lymph nodes and skin (secondary viremia) è replication in dermis (secondary skin lesions, high virus titers) From Spiesschaert et al, Vet. Res., 2011  Myxoma virus Clinical signs: (i) Californian rabbit (Sylvilagus bachmani) - localized fibromas (ii) European rabbit (Oryctolagus cuniculus) - lumps and large skin lesions - edema head & genitals - conjunctivitis è blindness - weeping (runny eyes) - fever, anorexia - secondary bacterial infections - death (2-14 days)  Myxoma virus Diagnosis: Clinical signs Histology: * Myxoma cells: Large stellate connective tissue cells with a large nucleus and abundant cytoplasm * Cytoplasmic inclusion bodies in epithelial cells  Myxoma virus Treatment and Control: No treatment Euthanasia of pet rabbits (painful death) Vaccination in UK with a live myxoma-vectored RHD vaccine è Australia: vaccination not allowed è US: vaccine is not readily available. So flea and mosquito control  Ectromelia General features: Genus Orthopoxvirus (same genus as vaccinia virus and variola virus) Causes mousepox. Natural mouse pathogen Only observed in mouse colonies kept for research. Can be endemic in mouse colonies, depending on mouse strain Infection through skin abrasions, via direct contact with contaminated fomites or other mice Depending on mouse strain: from local skin lesions (feet, snout, belly) to highly fatal (extensive necrosis)  Ectromelia Pathogenesis: (2) Primary viremia è liver and spleen (high titers, extensive necrosis) (1) Primary skin lesions (3) Secondary viremia è skin (generalized rash)  Ectromelia Clinical signs: Susceptible strains (eg. BALB/c): disseminated infection, rapid death (before virus shedding) Intermediate susceptible strains: develop skin lesions and disseminated infection, but survive long enough to shed virus (important for outbreaks!) Resistant strains (eg. C57/BL6): can spread the infection to other mice without showing clinical signs (important for outbreaks in mixed colonies) Primary skin lesions rash (14 days)  Ectromelia Diagnosis & control: Rapid and definitive diagnosis is important. Histology (necrosis in many tissues with cytoplasmic inclusion bodies), EM, or virus isolation Prevention and control is based on quarantine and import restrictions of contaminated material and mice Regular serological testing (ELISA) of valuable colonies Vaccination with vaccinia virus possible, but will interfere with ELISA testing (presence of antibodies)  Take home #2 Cowpox: rare in cattle. Zoonosis. Cats: from rodents (“crusty” lesions), humans: from cats (localized skin lesions) Fowlpox: 2 disease forms (skin lesions or diphtheritic membranes in URT). Bollinger bodies in cytoplasm Pseudocowpox: important for diff. diagnosis with FMD. Zoonosis (Farmyard pox) Orf virus: ecthyma contagiosum in sheep and goats. Proliferative lesions mainly on lips young animals. Zoonosis Myxoma virus: fatal disease in European rabbit (pet rabbits). Myxoma-vectored recombinant RHD vaccine Ectromelia: research mouse colonies. From local skin lesions to highly fatal (mouse strain dependent) Possible therapeutic options (based on mpox)