Marine Mammal Virology Flashcards

1
Q

Characteristic lesion of pox virus in bottlenose dolphins

A

Tattoo lesion (F8, Path book)

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2
Q

Most common herpesvirus in cetaceans

A

Gammaherpesvirus - Skin lesions, genital lesions, nephritis, encephalitis, disseminated infection (F8, Path book)

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3
Q

Describe the samples needed for viral isolation of the following viruses

  • Samples for morbilli-, herpes-, influenza-, parainfluenzaviruses:
  • Samples for pox-, papilloma-, calici-, and herpesviruses:
  • Samples for calici-, influenza-, and parainfluenzaviruses:
A
  • Samples for morbilli-, herpes-, influenza-, parainfluenzaviruses: brain, lungs, liver kidneys, spleen, LNs
  • Samples for pox-, papilloma-, calici-, and herpesviruses: cutaneous and mucocutaneous lesions
  • Samples for calici-, influenza-, and parainfluenzaviruses: nasal, oral, blowhole swabs
  • Molecular techniques are required for identification and characterization of papillomaviruses
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4
Q
A
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5
Q

Morbilliviruses are what type of viruses?

What morbilliviruses affect marine mammals?

What is their host range?

A
  • Enveloped viruses with intracytoplasmic replication, single-stranded RNA
  • Host range
    • Canine distemper virus (CDV)
      • Terrestrial origin
      • Caused repeated epidemics among Baikal seals, and Caspian seals in central Asia
    • Phocine distemper virus (PDV)
      • Variably susceptible
      • Most susceptible: North Atlantic harbor seals
      • Less susceptible: gray, harp, hooded seals
      • No evidence that Odobenidae (walruses) are susceptible
      • Otariids may also not be susceptible
      • Terio Pinnipedia
        • Several stranding peaks on the Atlantic coast of the US in harbor, harp, hooded, and gray seals
    • Cetacean morbillivirus (CeMV)
      • First recognized after epidemics among harbor porpoises and striped dolphins in Europe
      • Some mysticetes affected globally
      • Terio Cetacea - Several mass mortality events in odontocetes and mysticetes
      • Pilot whale morbillivirus (PWMV) – long-finned pilot whale in western North Atlantic
      • Beaked whale morbillivirus (BWMV) – Hawaii
      • CeMV-2 in Guiana dolphin from Brazil and Indo-Pacific bottlenose dolphins from Western Australia
      • CeMV-1 = Northern hemisphere; CeMV-2 = Southern hemisphere
    • Manatees
      • Only Florida manatee has been recorded with a morbillivirus mortality
    • Polar bears
      • Commonly exposed to PDV and CDV, but mortality has not been reported
    • Sea otters
      • Evidence of CDV infection in both northern and southern sea otters in Pacific Northwest and CA
      • Serology and PCR from Alaska suggests exposure to PDV-like virus
      • No reports of morbillivirus infection in marine otters from Peru and Chile
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6
Q

Describe teh clinical signs of morbillivirus infection in dolphins and phocid seals.

A
  • Clinical signs
    • Dolphins
      • Rarely described alive
      • Tremors, poor nutritional state (peracute infections may result in no weight loss), high burdens of ectoparasites and epibionts
    • Phocids
      • Pyrexia, serous or mucopurulent ocular and nasal discharges, coughing, mucosal cyanosis, dyspnea
      • If stranded, may develop pressure necrosis and high ectoparasite burdens
      • Swimming and diving may be impaired by interstitial pulmonary and SC emphysema
      • Hyperkeratotic dermatitis
      • Neuro signs – depression, lethargy, head tremors, convulsions, seizures
      • Pregnant females may abort
      • Terio pinnipeds
        • Oculonasal discharge, conjunctivitis, keratitis, coughing, dyspnea, diarrhea, abortion, head tremors, convulsions, and increased buoyancy
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7
Q

How are marine mammal morbillivurses diagnosed and treated?

A
  • Diagnosis
    • Characteristic gross and histopathology lesions
    • Immunohistochemistry can confirm viral antigen in lesions
    • Virus isolation and sequencing is gold standard
      • Or RT-PCR 🡪 sequencing
    • Terio Pinnipedia
      • Immunohistochemistry using cross-reactive monoclonal antibodies for morbillivirus nucleoprotein, detection via RT-PCR, antibody titers
    • Terio Cetacea
      • Virus isolation is gold standard
      • RT-PCR 🡪 sequencing
      • Serology useful for epidemiology
  • Therapy
    • Supportive
    • No vaccine against CeMV
    • Attenuate, inactivated, subunit CDV vaccines have been used in phocids
    • Recombinant CDV (monovalent recombinant canary pox vector expressing CDV antigens, Purevax) used in free-ranging Hawaiian monk seals
      • Seroconverted, no side effects
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8
Q

Describe the pathology of morbilliviruses in marine mammals.

What is the tropism for the viruses?

Where does viral replication occur?

What is the usual cause of death?

How do dolphins and phocid seals differ in their pathology?

A
  • Pathology
    • Predilection for lymphocytes, epithelial cells, neurons
    • Viral replication
      • In lymphoid organs in lymphoid organs 🡪 immunosuppression 🡪 predispose to other infections
      • Eosinophilic intracytoplasmic and intranuclear inclusion bodies
      • Skin, GI tract, respiratory tract, urogenital tract, CNS
    • Death usually from diffuse interstitial bronchopneumonia
      • Acute fatal infection: diffuse interstitial pneumonia and emphysema
      • Chronic infections: obscure viral lesions, septicemia, systemic mycoses
    • Cetaceans that cleared and resolved systemic dolphin morbillivirus (DMV) may have a chronic nonsuppurative encephalitis
    • Difference between phocids and odontocete
      • Pneumonia in phocids 🡪 severe interstitial emphysema tracking to fascia of the thorax and neck 🡪 inability to dive
      • Lungs of dolphins have large syncytial cells filling alveoli while the syncytia in phocids are smaller and less numerous
    • Terio Pinnipedia
      • Bronchointerstitial pneumonia, pulmonary atelectasis, congestion, edema
      • Often associated with secondary parasitic (pulmonary nematodiasis), bacterial, and concurrent viral infections
    • Terio Cetacea
      • Pneumonia with pulmonary consolidation and congestion, enlarged lymph nodes
      • CeMV is pancytopathic, but primarily associated with lesions of the respiratory, lymphoid, and CNS
      • Atypical chronic presentation: profound lymphoid depletion and fatal secondary infections
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9
Q

Describe the epidemiology of morbilliviruses in marine mammals.

What conditions are required for outbreaks?

What is the predominant route of transmission?

Is vertical transmission documented?

A
  • Epidemiology
    • Highly infectious
    • Require large populations of susceptible individuals
      • May persist in large spatial scale multihost ecosystems (possibly phocids of North Atlantic/Arctic)
    • No carrier state
    • Infection confers lifelong immunity
    • Replicates in epithelial cells of the skin, respiratory, GI, and urogenital tracts 🡪 shed via ocular, nasal, oral, or preputial secretions, shed epidermis, urine, and feces
    • Predominant route of horizontal transmission: respiratory
      • Facilitated by close proximity of pinnipeds at haul-out sides or odontocetes sharing expired air
    • Vertical transmission: rare in cetaceans, suspected for phocids
    • CeMV is endemic in gregarious odontocete species
      • Pilot whales, dusky dolphins, Fraser’s dolphins, melon-headed whales are reservoirs and vectors
    • Gregarious pinnipeds in large populations may act as reservoirs and vectors (gray and harp seals)
      • Absence or decrease of herd immunity 🡪 outbreaks of lethal, acute, subacute disease
    • DMV
      • Caused epidemics in common bottlenose dolphins along the US Atlantic coast
      • Bottlenose dolphins are infectious for 24 days (mean of 8 days)
      • Can transfer infection up to 220km away
      • Seasonal migrations facilitate wider dissemination
      • Mass mortalities in striped dolphins in the Mediterranean
        • Virus did not persist as an endemic infection afterwards
      • Occasional mortalities between epidemics are limited to dolphins with chronic encephalitis
        • Or sporadic introduction of virus into communities mostly protected by herd immunity
    • Terio Cetacea
      • Horizontal dissemination after inhalation of aerosolized virus shed by infected individuals
        • Close association of animals in cetacean pods
        • Migratory behavior promotes transmission
      • CeMV-infected females may transmit transplacentally to fetuses and neonates during lactation
  • Public health significance
    • No known human risk
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10
Q

Describe parainfluenzavirus infections in marine mammals.

What is the host range?

Parainfluenza viruses are what type of virus?

What clinical signs are seen with infection?

What lesions are present on necropsy?

How prevalent is exposure to this virus?

Is there public health risk?

A

Parainfluenzaviruses

  • Host range
    • Isolated from a captive bottlenose dolphin 🡪 serologic studies found antibodies in captive and free-ranging bottlenose dolphins from CA and FL
  • Virology
    • Genus Respirovirus
    • Enveloped, single-stranded RNA
    • Intracytoplasmic replication
    • T. truncatus parainfluenza virus type 1 (TtPIV-1) showed common ancestry with bovine PIV-3 genotype B
  • Clinical signs
    • Captive 19yo male Atlantic bottlenose dolphin with TtPIV-1
      • Dyspnea, raspy malodorous breath, purulent blowhole exudate
      • Seroconversion demonstrated posthumously
      • Additional 22 captive dolphins had similarly abnormal hemograms to the fatal case
        • Some had anorexia, lethargy, and respiratory/ocular clinical signs
        • 23% of animals showed no clinical signs
  • Therapy
    • Supportive
  • Pathology
    • Focally extensive pyogranulomatous broncho-interstitial pneumonia with intralesional yeast organisms with multifocal erosive and ulcerative laryngotracheitis
  • Diagnosis
    • Isolated on Vero cells using antemortem lung aspirates and necropsy tissues
    • ELISA developed for serology
  • Epidemiology
    • 7.1% prevalence of antibodies in free-ranging dolphins in Sarasota, FL
    • 15.5% prevalence of antibodies in managed dolphins from the Navy
    • Age at seroconversion differed: free-ranging at 11.5 years, managed at 20.7 years
  • Public health significance
    • Potential b/c PIV-3 infects several terrestrial species, including humans
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11
Q

What type of virus is influenza?

What species of marine mammals have been infected?

What species have had seropositivity?

What are typical clinical signs?

Is there any therapy?

A

Influenzaviruses

  • Host range
    • Harbor seals most clinically susceptible (mass mortalities)
    • Pandemic influenza H1N1 detected in healthy northern elephant seals, harbor seals and California sea lions in CA, northern sea otters in Washington
    • Influenza A seropositivity in common minke whales, Dall’s porpoises, belugas
    • Influenza B (virus of humans, no wildlife reservoir) detected in healthy harbor and gray seals, Caspian seals, South American fur seals
  • Virology
    • Family Orthomyxoviridae
    • Enveloped, linear, RNA viruses
    • Intranuclear replication
    • Only influenza A and B have been found in marine mammals
    • Majority of influenza A isolates from baleen whales and pinnipeds were derived from waterfowl adapted strains
  • Clinical signs
    • Influenza A: epidemics of fatal respiratory disease in harbor seals from US and Europe
      • Conjunctivitis, frothy or blood-tinged nasal discharge, SC emphysema of the thorax and neck, weakness, incoordination
    • Infection in northern elephant seals, California sea lions, Pacific harbor seals, northern sea otters with H1N1 was subclinical
    • Pilot whale with 2 influenza A viruses: emaciated, swam with difficulty
    • 2 harbor seals with influenza B virus had dyspnea, but also had parasitic pneumonia
    • Terio pinnipeds
      • Dyspnea, nasal discharge, lethargy, emphysema
  • Therapy
    • Supportive
    • No vaccines
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12
Q

What are the typical lesions associated with influenza infections in marine mammals?

How is influenza diagnosed?

What are the zoonotic risks?

A
  • Pathology
    • Harbor seals
      • Diffuse hemorrhagic pneumonia
        • Necrotizing bronchitis, bronchiolitis, hemorrhagic alveolitis
      • Regional lymph nodes enlarged, edematous, hemorrhagic
    • Pilot whale
      • Hemorrhagic lungs, enlarged hilar lymph nodes
    • Terio pinnipeds
      • Partially collapsed lungs, pulmonary congestion, necrotizing bronchitis and bronchiolitis, hemorrhagic alveolitis, bronchial gland adenitis, occasionally interstitial pneumonia
  • Diagnosis
    • Clinical signs, gross and histopathology, immunohistochemistry
    • Pilot whale and harbor seal influenza A viruses isolated after inoculation of tissue suspension and/or lung and throat swab samples
    • Serology using hemagglutination and indirect and competitive ELISAs
    • Terio pinnipeds
      • ELISA, immunohistochemistry using influenza A virus nucleoprotein-specific monoclonal antibody and RT-PCR in lung and throat swabs
  • Epidemiology
    • Influenza A
      • Occurs sporadically in marine mammals
      • Caused by viruses adapted to waterfowl and seabirds
      • Direct transmission by birds is most probable route of infection
        • Shed by oral and fecal routes
      • Do not seem to be maintained endemically in marine mammal populations
      • Incubation period: <3 days
    • H1N1pan09, H3N2 and Influenza B
      • Possible human 🡪 pinniped
      • H1N1 exposure in northern sea otters is of unknown source – may have been through contact with northern elephant seals
  • Public health significance
    • Influenza A and B are serious human pathogens
    • Seal influenza A 🡪 humans
      • During necropsies 🡪 caused keratoconjunctivitis within 2-3 days of exposure
      • Infected seal sneezed in face of handler 🡪 conjunctivitis
      • All affected people recovered within 7 days, none developed antibody titer
      • Replicated in the lungs and nasopharynx of squirrel monkeys after intratracheal administration
    • Need biosafety measures
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13
Q

What type of virus are coronaviruses?

What are the four genera and their species affinity?

What marine mammals have been affected and what clinical signs were observed?

What were the lesions found on necropsy?

A

Coronaviruses

  • Host range
    • Detected during mortality investigation in managed harbors seals at an aquarium in Florida and in free-ranging harbor seals in CA
    • Isolated from managed beluga and from feces of 3 Indo-Pacific bottlenose dolphins
  • Virology
    • Enveloped, positive-strand linear RNA
    • Intracytoplasmic replication
    • 4 genera: alpha-, beta-, gamma-, delta-
      • Alpha- and beta- in mammals
      • Gamma- and delta- in birds
    • Seal CoV
      • Alpha- genus
      • Closely related to feline, canine, ferret, swing CoVs
    • Beluga CoV (BWCoV) and bottlenose dolphins coronavirus (BdCoV)
      • Gamma-
      • “cetacean coronavirus”
  • Clinical signs
    • 2/3 managed harbor seals died without clinical signs
      • 1 had leukocytosis, dehydration, hypernatremia, hyperchloremia
    • Pacific harbor seals found dead
    • Managed beluga had hepatic and respiratory failure
  • Therapy
    • Supportive
  • Pathology
    • Managed harbor seals: acute necrotizing enteritis and pulmonary edema
    • Pacific harbor seals: pulmonary congestion, hemorrhage, and consolidation
      • Histopath: necrotizing lymphocytic and histiocytic lobar pneumonia with intralesional bacteria
    • Beluga
      • Severe, multifocal, coalescing centrilobular-to-massive acute hepatic necrosis
  • Diagnosis
    • Indirect fluorescent antibody staining
    • RT-PCR 🡪 sequencing
  • Epidemiology
    • Cetacean CoVs may have an avian origin (because they are gamma-)
  • Public health significance
    • No known risk
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14
Q

What type of viruses are caliciviruses?

What genera of caliciviruses infect marine mammals?

What is the natural host of San Miguel Sea Lion Virus?

How did these viruses end up causing Vesicular Exanthema of Swine?

What are the clinical signs of pinniped vesiviruses? Where do these lesions usually occur?

How do cetacean visiviruses present?

How do noroviruses and sapoviruses affect marine mammals?

How are these viruses treated?

A

Caliciviruses

  • Host range
    • >20 serotypes of marine vesiviruses from Pacific marine mammals
    • Noroviruses and sapoviruses detected in harbor porpoises and California sea lions
  • Virology
    • Non-enveloped single-stranded RNA viruses
    • Intracytoplasmic replication
    • Vesivirus, Norovirus, Sapovirus, Lagovirus, Nebovirus
    • Vesiviruses
      • Ex. San Miguel Sea Lion Virus (SMSV)
      • Most are strains of the same virus species: vesicular exanthema of swine virus (VESV)
      • 2 others from pinnipeds (SMSV-8 in northern fur seals and SMSV-12 from CA sea lions and northern fur seals) are genetically distinct from VESV
    • Sapoviruses and noroviruses
      • 2 sapoviruses detected in feces of California sea lions
      • Harbor porpoise norovirus found – similar to one detected in oysters
    • Terio pinnipeds
      • 40 serotypes of vesivurses
      • Opal eye perch are a likely natural host
      • Indistinguishable from caliciviruses causing swine vesicular exanthema
        • Feeding swing uncooked garbage with marine mammals and fish was a likely route of introduction into the swine population
      • Zoonotic
        • Human vesicular dermatitis and flu-like illness after lab and field exposures
  • Clinical signs
    • Pinniped vesiviruses
      • Epidermal vesicles on non-haired skin
      • Most commonly on flippers and remain longest on the dorsal aspect
      • Range from 1-3 cm and may coalesce to form bullae 🡪 erode 🡪 shallow, fast-healing ulcer 🡪 plaque-like scar
      • Can resolve completely within 9 weeks
      • In managed California sea lions, resolve in 4-20 days
      • Vesicular and non-vesicular lesions can occur on buccal mucosa, nasal planum, and other mucocutaneous junctional areas
      • Premature parturition observed in California sea lions also infected with leptospirosis
        • Premature pups had respiratory distress and locomotor difficulties, did not survive
      • Experimentally-infected northern fur seal pups 🡪 interstitial pneumonia and mild encephalitis (virus could not be recovered)
      • Terio pinnipeds
        • Vesicular dermatitis that progresses to ulceration primarily of the nonhaired surfaces of the flippers
        • Necrosis of underlying digits can occur
        • Ulcerative stomatitis and ulcerative and nodular dermatitis of the lips, nasal planum, chin in CA sea lions
        • Abortion and premature birth in CA sea lions
    • Cetacean vesiviruses
      • Isolated from skin vesicles developed on tattoo skin lesions
      • Vesicles quickly eroded 🡪 shallow ulcers
    • Noroviruses and sapoviruses – not associated with any clinical signs
  • Therapy
    • Most resolve without supportive treatment
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15
Q

What lesions on pathology are observed with marine mammal caliciviruses?

How are caliciviruses diagnosed?

Describe the epidemiology of pinniped vsiciruses. What vectors may be involved?

Are their any public health concerns with marine mammal caliciviruses?

A
  • Pathology
    • Vesiviruses
      • Viral replication in the stratum spinosum 🡪 necrosis and formation of intraepidermal vesicles 🡪 rupture 🡪 exposed basal layer
      • In cats, tropism for alveolar macrophages – may be similar in some neonatal pinnipeds
      • Terio pinnipeds
        • Without formation of inclusion bodies
        • Vesicles are very transient and ulcers with secondary bacterial infections are common
    • Noroviruses
      • Porpoise norovirus replicates in the cells of the intestinal tract, lesions not described
  • Diagnosis
    • Vesivirurses
      • Originally detected via virus isolation in cell cultures, electron microscopy, indirect immunofluorescence
      • rtRT-PCR, ELISA developed
      • Terio pinnipeds – culture or RT-PCR (can identify most serotypes and differentiate them from reportable vesicular diseases)
    • Noroviruses
      • Detected by random PCR, ELISA developed
  • Epidemiology
    • Vesiviruses
      • California sea lions, opaleye perch involved in maintenance in the North Pacific Ocean
        • Virus can remain viable for at least 32 days in opaleye perch
        • By the time a California sea lion is 4mo, they have antibodies
      • Reservoir in the Arctic not known
      • Not detected in marine mammals outside the North Pacific and Arctic
      • Horizontal transmission by direct contact, may be vector mediated
        • Metazoan parasites like liver fluke Zalophotrema and lungworm Parafilaroides may be mechanical vectors
        • Direct transmission to terrestrial mammals scavenging on carcasses
      • Endemic infection in northern fur seals on Pribilof Islands
      • May be infected by viruses of terrestrial origin
        • Reptile, mink, cattle viruses found in managed pinnipeds
      • Marine vesiviruses were causative agent of vesicular exanthema of swine outbreaks in the US
        • Fed swine raw garbage contaminated with marine mammal and fish products (1930-50)
    • Noroviruses
      • Prevalence 10.4% in intestinal tissue from 48 harbor porpoises stranded in the Netherlands in 2006-15
  • Public health significance
    • Vesiviruses
      • VES in pigs resembles foot and mouth disease – classified as a foreign animal disease (FAD)
      • No confirmation that marine caliciviruses cause clinical disease in people
        • But can infect a wide host range
        • May cause blisters on hands, feet, cornea
    • Noroviruses
      • Harbor porpoise norovirus is very similar to that from oysters 🡪 concern for zoonotic potential
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16
Q

What type of viruses are herpesviruses?

What alphaherpesviruses and gammaherpesviruses affect marine mammals?

What are the clinical signs associated with phocid herpesvirus 1?

What about otarrid herpesvirus 1?

What about otarrid herpesvirus 3?

A

Herpesviruses

  • Host range
    • Alpha- and gamma- in managed and free-ranging pinnipeds and cetaceans
    • Also found in sea otters
    • Trichechid herpesvirus 1 (TrHV1) from skin and blood buffy coats from Florida manatees
  • Virology
    • Enveloped, double-stranded DNA viruses
    • Intranuclear replication in reptiles, birds, mammals
    • Can establish latent state and reactivate following psychological or physical stressors
    • 3 subfamilies (Alpha-, beta-, gamma-)
      • Alpha- are neurotropic with a variable host range
        • Genera: Simplexvirus, Varicellovirus, Scutavirus, Mardivirus, Iltovirus (last 2 in birds)
      • Gamma- are lymphotropic, specific or either T or B lymphocytes
        • Genera: Lymphocryptovirus, Rhadinovirus, Percavirus, Macavirus – infect mammals
      • All from cetaceans or pinnipeds are alpha- or gamma-
    • Phocid herpesvirus 1 (PHV-1) is the only alpha- recognized in pinnipeds (several in odontocetes)
    • Odontocete herpesviruses are likely cetacean-specific
    • Otariid HV-1 (California sea lion) and OtHV-4 (northern fur seal) belong to their own clade
    • TrHV1 in manatees is a gamma-, clusters with viruses from elephants, tapir, hyrax
  • Clinical signs
    • Alphaherpesviruses
      • Several cetacean species: encephalitis, acute necrotizing lesions in multiple organ systems, nephritis, genital ulcers, dermatitis
      • Terio cetaceans
        • Seen less frequently than gammaherpesviruses
        • Lesions vary from incidental to acute, systemic necrotizing inflammation in multiple organ systems
    • Gammaherpesviruses
      • Oral lesions, genital ulcers, plaques, wart-like lesions in various cetaceans
        • Unknown if the gammaherpesviruses cause the genital lesions
      • Terio cetaceans
        • Associated with skin lesions, genital lesions, nephritis, encephalitis, and disseminated infections
    • Outbreaks of acutely fatal generalized PHV-1 in neonatal harbor seals in rehabilitation
      • Fatal disseminated infection can also occur in adult harbor seals
      • Ocular and nasal discharge, dyspnea, gingivitis, vomiting, diarrhea, pyrexia, lethargy, anorexia
      • Neonates: liver and adrenal glands*
        • Marked lymphopenia from adrenal insufficiency
      • Terio pinnipeds
        • Isolated from harbor and gray seals in Europe and from both North American coasts
        • High morbidity and mortality
        • Outbreaks in rehabilitation facilities
        • Clinical disease and fatal generalized infection most common in neonates and young pups
        • Horizontal transmission via direct contact and aerosols
        • Vertical transmission has been reported
    • OtHV-1
      • Multifactorial urogenital carcinoma in California sea lions
      • Clinical signs related to obstruction of lymphatic drainage (perineal and hind limb edema) and obstruction of ureters (hydronephrosis and terminal renal failure)
      • Metastases occur in lungs, liver, kidney, spleen, regional lymph nodes
      • Terio OtHV-1
        • Amplified via PCR from CA sea lions with urogenital carcinoma
        • Considered likely factor in tumor development
        • Can be amplified from urogenital tract, less frequently the oral cavity with no clinical evidence
        • Prevalence higher in adults than juveniles
        • Sexual transmission thought to occur
        • Females may transmit virus to pups during birth
        • OtHV-3
      • Geriatric male California sea lion with OtHV-3 died from acute lymphoblastic leukemia
    • May be associated with ocular lesions in pinnipeds
17
Q

What lesions are associated with herpesviral infections in marine mammals?

Particularly phocid herpesvirus 1, otarrid herpesivirus 1 and 3?

What are the inclusion bodies?

How is the disease diagnosed?

How prevalent are herpesviruses in wild marine mammals?

A
  • Therapy
    • No vaccines
    • Acyclovir in neonatal harbor seals
  • Pathology
    • Fatal herpesviral encephalitis in harbor porpoises, bottlenose, and striped dolphins from eastern Atlantic
      • Neuronal necrosis, intranuclear acidophilic inclusions
    • Cutaneous and mucosal lesions
    • Belugas in Canada – multifocal necrotizing dermatitis with circular depressed lesions
    • Bottlenose dolphins in Florida – proliferative dermatitis with intranuclear inclusion bodies
    • Hyperplastic genital plaques and mucocutaneous lesions in harbor porpoises, bottlenose dolphins, killer whale, Risso’s dolphin, Blainville’s beaked whale – gammaherpesvirus
    • PHV-1 (alpha)
      • Epidemic pneumonia in a rehab center in Europe
      • Focal coagulative necrosis of the adrenal cortex and liver in Pacific harbor seals
      • Terio
        • Most common lesions: adrenocortical and hepatic necrosis
        • Adrenal necrosis may be associated with mineralization
    • PHV-2 (gamma) not associated with clinical disease in harbor seals
      • Isolated from an adult female gray seal with dermatitis
    • OtHV-1 – described elsewhere
    • OtHV-4 – not associated with neoplasia or any other pathology, lacks oncogenes of OthV-1
    • OtHV-3 – fatal acute lymphoblastic leukemia in a California sea lion
      • Herpesviral particles seen by electron microscopy in lymphocytes in esophagus
    • Both cetacean gamma- and papillomaviruses detected in cells of genital papillomas or wart-like lesions
  • Diagnosis
    • Amphophilic intranuclear inclusions
    • PCR, electron microscopy
    • PHV-1 and -2 initially isolated from host tissues
    • Tissue culture replaced with nested PCR and qPCR or in situ hybridization on fixed tissues
    • Terio
      • Virus isolation, PCR, IHC, and serology (ELISA) used to diagnose
  • Epidemiology
    • Over 50% of stranded belugas had BoHV-1
    • Infections in cetaceans probably increase with age and become latent
    • In manatees, TrHV-1 has prevalence of 45% in healthy animals
    • Serological surveys show wide geographical distribution
    • Physiologic stress and/or immunosuppression associated with recrudescence
    • OtHV-1
      • Presence in epithelial cells of the lower urogenital tract in California sea lions and higher prevalence in adult animals 🡪 suggests horizontal mode of sexual transmission
      • Higher prevalence in stranded CA sea lions (34.9%) compared with managed (12.5%) animals
    • OtHV-4 – prevalence of 32% in free-ranging female northern fur seals
  • Public health significance
    • Not known to be zoonotic
18
Q

What type of virus are poxviruses?

What poxviruses affect marine mammals? How are they geographically distributed?

What are the typical clinical signs in cetaceans and pinnipeds? Where are the lesions typically located?

A

Poxviruses

  • Host range
    • Cetacean poxviruses detected worldwide
    • Pinniped parapoxviruses are ubiquitous and found in most regions where phocids and otariids occur
      • NOT found in free-ranging Australian, New Zealand, or South African pinnipeds
    • New species of pox caused raised, often ulcerated, skin lesions in Steller sea lion pups
    • Non-parapoxvirus detected in gray seals with skin nodules during a PDV outbreak in Netherlands
  • Virology
    • Enveloped, double-stranded DNA viruses
    • 2 subfamilies
      • Chordopoxvirinae in vertebrates
      • Entomopoxvirinae in invertebrates
    • Genus Parapox found in marine mammals
      • Pinniped poxviruses may be classified to habitats (ie Pacific or Atlantic)
    • Genus “cetacean poxvirus” (CPV) awaiting acceptance
      • 6 separate clusters
      • Cetacean poxvirus-2 (CPV-2) only in mysticetes
  • Clinical signs
    • Cetacean poxvirus causes tattoo skin disease
      • Typical, irregular, gray/black/yellowish, cutaneous lesions with stippled pattern
      • May persist for months or years
      • Recurrence possible
      • Does not seem to have marked negative health impact
        • Extensive lesions and fatal outcomes have been reported
      • Terio cetaceans
        • Non-proliferative skin lesions present for extended periods of time
        • Seen in bottlenose dolphins, killer whales, harbor porpoise, short and long-beaked common dolphins, Commerson dolphins, striped dolphins, white-beaked dolphins, Pacific white-sided dolphins, dusky dolphins, Burmeister’s porpoise, short and long-finned pilot whales, Southern right whales, bowhead whale
        • Foci of hyperpigmented skin variously presenting as pinpoint, ring, and serpiginous patterns
        • Contiguous with the healthy skin surface
        • Pinpoint lesions have a dark center surrounded by a pale margin forming a target lesions
        • Flippers and flukes generally less affected
        • Often wax and wane over months and years
        • Marked reduction in lesion intensity noted with warmer water temperatures
        • Anthropogenic factors may promote expression of infection
        • Lesions commonly occur adjacent to or directly associated with areas of skin damage from conspecific trauma
        • Inflammation is not a feature of these lesions
    • Pinnipeds with parapoxvirus
      • Firm, raised skin nodules that may ulcerate
      • Especially on the head, neck, and flippers, oral cavity
      • Heal spontaneously over a few weeks to 9 months 🡪 leaves slightly raised, gray, alopecic scar
      • Mucosal lesions may cause loss of appetite in pups
      • Terio
        • Skin and mucosal lesions from numerous species (CA sea lions, South American sea lions, Steller sea lions, northern fur seals, harbor and gray seals)
        • Transmission through direct contact (rubbing or biting)
        • Lesions may develop during times of stress or concurrent diseases
        • Raised, firm, sometimes ulcerated nodules along the head, neck, andthorax
        • Nodular or plaque-like lesions may occur along tongue and oral commissure
        • Lesions will often spontaneously regress
        • Zoonotic – causes nodular cutaneous lesions in humans, transmission when virus enters broken skin
    • Sea otters
      • Slightly raised, ulcerated plaques on a northern sea otter
      • Regressed over a 2 month period
19
Q

What are the lesions associated with marine mammal poxviruses?

What are the inclusion bodies?

How are these diseases diagnosed adn treated?

Describe the epidemiology of marine mammal poxviruses - what groups are more commonly affected?

Are there any public health concerns?

A
  • Therapy
    • Managed cetaceans: improved husbandry, adequate water temperatures and sun exposure, low population density
    • Lesions in pinnipeds and sea otters usually self-limiting, but may have bacterial infection
      • Tried cidofovir in California sea lions
  • Pathology
    • Cetaceans
      • Focal swelling and vacuolar degeneration
      • In chronic lesions, focal pitting and disruption of the surface layer 🡪 allows entry of bacteria and other opportunists
    • Pinnipeds
      • Exophytic or proliferative hyperkeratotic and parakeratotic growth of the stratum spinosum and corneum
      • Bollinger-type cytoplasmic inclusions
      • Terio pinnipeds
        • Histologically: marked epidermal and follicular hyperplasia
  • Diagnosis
    • Cetaceans
      • Stippled pattern and concentric growth of tattoo skin lesions is characteristic
    • Pinnipeds
      • Most often seen as outbreaks where large numbers of pups or juveniles are housed
    • Sea otters
      • Raised plaques on skin or buccal labia that ulcerate centrally
  • Epidemiology
    • Cetaceans
      • Worldwide
      • Higher prevalence in juveniles than in adults (healthy)
        • High percentage of adults had acquired active immunity after infection
      • If in poor health, adults had higher prevalence
      • In managed animals, males seem to be more vulnerable
    • Pinnipeds
      • Antibodies detected in 91% of free-ranging California sea lions
        • Nursing pups had 98-100% seroprevalence – early infection or maternal immunity
      • Outbreaks often occur in rehabilitated pinnipeds
      • Incubation period: 1-5 weeks
      • Stress and immunosuppression may favor development of clinical signs
  • Public health significance
    • *Pinniped parapoxviruses are zoonotic*
      • Nodular lesions, often painful, evolve slowly
      • Fever, myalgia, fatigue
    • Cetacean poxviruses do NOT infect humans
20
Q

What type of virus are papillomaviruses? What ones affect marine mammals?

What are the typical clinical signs?

How does that differ between sirenians and cetaceans?

A

Papillomaviruses

  • Host range
    • Generally host- and site-restricted
    • Detected by molecular techniques in cutaneous and genital warts of many cetacean species, gastric papillomas of belugas
  • Virology
    • Non-enveloped, double-stranded DNA virus
    • All cetacean papillomaviruses groups into the genera Omikronpapillomavirus and Upsilonpapillomavirus except for Phocoena PV-3
    • Zalophus californianus papillomavirus 1 (ZcPV1) is in the same clade as canine PV-3 and PV-4, genus Chipapillomavirus
    • 4 manatee PVs cluster in Rhopapillomavirus genus
  • Clinical signs
    • Cutaneous, genital, and lingual warts and papillomas
    • Lesions are single or multiple, and may grow to large dimensions
    • Dolphins and porpoises – genital PVs are white, gray, black, or pinkish; slightly raised; oval or circular warts; irregular folded or velvety surface
    • Cutaneous warts in odontocetes – raised, smooth, or velvety
    • TmPV-1 (Trichechus manatus, Florida mantees) – multiple, white, round, superficial, sessile, 2-5mm diameter lesions in preputial ostium
    • ZcPV1 (Zalophus californianus, CA sea lion) – proliferative, white to pink, often raised, 1-5mm papillomas on the axilla, underside of the tail, and prepuce
    • Bottlenose dolphins with papillomas – hypoferremia, hyperglobulinemia, hyperalphaglobulinemia – acute phase response
    • Terio Sirenia
      • Trichechus manatus latirostris papillomaviruses (TmPV)
      • Hyperplastic skin lesions in managed FL manatees
      • Largely historical and associated cutaneous lesions not described in free-ranging animals
      • Variably multifocal, pedunculated, whitish-gray, verruciform or filiform papillomas over the head and leading contact regions of the pectoral flippers to more diffuse and numerous sessile, solid papillomas with a different distribution
        • Appear to coincide with preexisting areas of superficial trauma, such as scratch marks
      • Possible viral latency and immunologic suppression
    • Terio Cetacea
      • Proliferative mucosal and cutaneous lesions in free-ranging and managed
      • Serologic positivity to PV higher in free ranging dolphins (90%) compared with managed (51%)
      • ELISA reactivity higher in males than females
      • Mean age of free-ranging dolphins with papillomas is 11 years; 30 years in managed care
      • Transmission likely horizontal with orogenital development early in life in free-ranging animals
      • PV-associated mucosal lesions are typical
        • Orogenital predilection with tropism for vulvar and vaginal mucosa, penile mucosa, oral or esophageal mucosa, frequent involvement of frenulum of the tongue
        • Less commonly skin
      • Seen in harbor porpoises, killer whales, pilot whales
      • Lesions can be warty and/or plaque-like, singular or multiple, and coalescing
21
Q

What treatments exist for marine mammal papillomaviruses?

What lesions are typically found on pathology?

Describe teh epidemiology of these diseases in the wild - how common are they?

A
  • Therapy
    • No specific treatment
    • May persist for many years, regress over months to years, or undergo neoplastic transformation
    • Bottlenose dolphins with orogenital papillomas
      • Co-occurrence of benign papillomas and squamous cell carcinoma – suggests neoplastic transformation
    • Vaccine
      • Potential antigen for TtPV vaccine, but no further progress
      • Supposedly a recombinant vaccine candidate for manatee PV1 has been developed
  • Pathology
    • Bottlenose, common, dusky dolphins
      • Orogenital sessile papillomas are plaques of uniformly proliferating, keratinocytes
      • Inclusion bodies not observed
      • PV antigen detected by immunohistochemistry
      • Terio Cetacea – epithelial hyperplasia
    • Manatees
      • More exophytic growth pattern
    • Pinnipeds
      • Marked hyperkeratosis, no viral inclusions observed
  • Diagnosis
    • Gross and histo features
    • Confirmation by immunohistochemical staining
    • PCR
    • Terio Sirenia (TmPV)
      • Confirmed by sequencing DNA from suggestive lesion
      • IHC for bovine papillomavirus
  • Epidemiology
    • Genital papillomas observed in 66.7% of dusky dolphins and 48.5% of Burmeister’s porpoises in Peru, 30% of bottlenose dolphins in Cuba
    • TtPV-1 antibody prevalence in managed (51%) and free-ranging (90%) bottlenose dolphins – suggests venereal transmission
      • Males have higher prevalence
    • Cutaneous papillomas less frequently reported in odontocetes
    • Antibodies against TmPV-1 found in 26.3% of managed and free-ranging manatees in FL
      • Free-ranging manatee rarely had lesions
      • Papillomas were common (72.7%) in seropositive managed animals – stress and immunosuppression?
  • Public health significance
    • No zoonotic risk
22
Q

What type of viruses are adenoviruses?

Adenoviruses affect what marine mammals?

Describe the clinical signs associated with adenoviral infection in marine mammals.

A

Adenoviruses

  • Host range
    • Isolated from GI samples from sei and bowhead whales, belugas, bottlenose dolphins, harbor porpoises
    • Recovered from CA and South American sea lions, South African and South American fur seals, Pacific harbor, northern elephant, and Hawaiian monk seals
    • In mustelids, canine adenovirus-1 found in managed Eurasian otters and a novel adenovirus in southern sea otters
  • Virology
    • Non-enveloped, double-stranded DNA viruses
    • Intranuclear replication
    • All marine mammal adenoviruses belong to genus Mastadenovirus
    • California sea lion adenovirus 1 (CSLAdV-1 or OtAdV-1) from stranded sea lions
    • PhAdV-1 (northern elephant seal), PhAdV-2 (Pacific harbor seal) closely related to each other
    • OtAdV-2 is distantly related to all Mastadenovirus species
    • Tursiops adenovirus-1 found in 4 managed bottlenose dolphins with gastroenteritis
    • Terio
      • Sporadically in CA sea lions
      • Recently associated with an outbreak involving multiple otariids in managed care
  • Clinical signs
    • California sea lions
      • Died in rehabilitation
      • Weak, emaciated, photophobic, abdominal pain, intermittent and progressive blood-tinged diarrhea, leukopenia, monocytosis
    • Managed pinnipeds in Japan
      • Diarrhea, lethargy, elevated AST and ALT, died after 3 days
    • OtAdV-1 concurrent with diarrhea and anorexia in managed and stranded California sea lions
    • OtAdV-1 not associated with disease in a managed Hawaiian monk seal
    • Managed bottlenose dolphins
      • Anorexia, diarrhea, vomiting, no changes to serum or hematological values
23
Q

What lesions are found with adenoviral infections in marine mammals?

How is this disease diagnosed?

Are there any treatments?

How is this transmitted? Are these viruses host specific?

A
  • Therapy
    • Supportive
    • No vaccines
    • Killed CAdV-1 vaccine protected American black bears may be an approach for managed pinnipeds
  • Pathology
    • Yearling California sea lions in rehabilitation
      • Systemic viral replication with intranuclear inclusion bodies in endothelial cells
    • South American sea lion – intranuclear inclusion bodies in hepatocytes and enterocytes
    • Hawaiian monk seal – intranuclear inclusion bodies in hepatocytes
    • Terio pinnipeds
      • Most common lesion: multifocal necrotizing hepatitis with hepatocellular intranuclear inclusions
      • Ocular lesions include corneal edema, keratitis, iridocyclitis
      • Several cases of necrotizing enteritis in CA sea lions
  • Diagnosis
    • Light and electron microscopy to detect viral inclusion bodies
    • Serological tests against CAdV-1 and -2 in managed bottlenose dolphins
    • Isolated in various cell lines
    • PCR in feces and in formalin fixed tissues
    • Terio pinnipeds
      • Amplified via PCR from liver and feces in affected individuals
      • Adenoviral particles seen via transmission electron microscopy
      • Amplified from feces of individuals without evidence of clinical disease (some may be subclinical shedders)
  • Epidemiology
    • Narrow host range
      • Restricted to 1 species and close relatives
    • Some CAVs and otarine AdV have a broader host range
    • OtAdV-1 in managed and free-ranging pinnipeds from Asia and North America
    • Outbreaks among managed animals suggest fecal-oral mode of transmission
    • Prevalence of OtAdV-1 in fecal samples from free-living CA sea lions is similar to that of managed animals
    • 29% of archival tissues from southern sea otters 🡪 endemic infection
  • Public health significance
    • No zoonotic risk