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Rhabdovirus Nearly 100% fatal after symptoms appear Bullet shaped virion Helical nucleocapsid Zoonotic Glycoprotein Binds to Nicotinic Ach receptors in the post-synaptic junction. Replicates in motor neurons and move retrograde Incubation weeks to months – 1-3mm/day tingling and muscle spasm, dorsal root ganglia Biopsy and autopsy, Negri body – eosinophilic inclusion Pyramidal cells of hippocampus and Purkinje cells Passive immunization and active vaccination Wake up with bat, vaccination
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Rhabdovirus - smbs.buffalo.edu · Rhabdovirus • Nearly 100% fatal after symptoms appear • Bullet shaped virion • Helical nucleocapsid • Zoonotic • Glycoprotein Binds to

Feb 12, 2019

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Page 1: Rhabdovirus - smbs.buffalo.edu · Rhabdovirus • Nearly 100% fatal after symptoms appear • Bullet shaped virion • Helical nucleocapsid • Zoonotic • Glycoprotein Binds to

Rhabdovirus

• Nearly 100% fatal after symptoms appear• Bullet shaped virion• Helical nucleocapsid• Zoonotic• Glycoprotein Binds to Nicotinic Ach receptors in the post-synaptic junction.

Replicates in motor neurons and move retrograde• Incubation weeks to months – 1-3mm/day tingling and muscle spasm, dorsal root

ganglia• Biopsy and autopsy, Negri body – eosinophilic inclusion• Pyramidal cells of hippocampus and Purkinje cells• Passive immunization and active vaccination

• Wake up with bat, vaccination

Page 2: Rhabdovirus - smbs.buffalo.edu · Rhabdovirus • Nearly 100% fatal after symptoms appear • Bullet shaped virion • Helical nucleocapsid • Zoonotic • Glycoprotein Binds to

Negri Body and EM of Rabies Virus

Page 3: Rhabdovirus - smbs.buffalo.edu · Rhabdovirus • Nearly 100% fatal after symptoms appear • Bullet shaped virion • Helical nucleocapsid • Zoonotic • Glycoprotein Binds to

Recent Rabies Case in Florida

• Man capture bat• Puts in on porch in container and tells his 6 year old son not to touch

it

Page 4: Rhabdovirus - smbs.buffalo.edu · Rhabdovirus • Nearly 100% fatal after symptoms appear • Bullet shaped virion • Helical nucleocapsid • Zoonotic • Glycoprotein Binds to

Polio

• Naked• Acid Stable• Replicates in Peyer’s patches in ileum then disseminate to:• Anterior horn cells • Asymmetric• Three serotypes

Page 5: Rhabdovirus - smbs.buffalo.edu · Rhabdovirus • Nearly 100% fatal after symptoms appear • Bullet shaped virion • Helical nucleocapsid • Zoonotic • Glycoprotein Binds to

http://sphweb.bumc.bu.edu/otlt/mph-modules/ph/polio/mobile_pages/polio_new2.html

Page 6: Rhabdovirus - smbs.buffalo.edu · Rhabdovirus • Nearly 100% fatal after symptoms appear • Bullet shaped virion • Helical nucleocapsid • Zoonotic • Glycoprotein Binds to

Polio vaccine

• Salk• Killed virus• No IgA response• NO RISK of reversion to paralytic polio• NO HERD effect

• Sabin• Oral, three serotypes of attenuated polio• Has herd effect• Produces IgA• CAN revert to paralytic polio

• US uses only Salk now

Page 7: Rhabdovirus - smbs.buffalo.edu · Rhabdovirus • Nearly 100% fatal after symptoms appear • Bullet shaped virion • Helical nucleocapsid • Zoonotic • Glycoprotein Binds to

Non-Polio Enteroviruses

• Many different serotype• viral conjunctivitis• hand, foot, and mouth disease• meningitis • pericarditis • acute flaccid paralysis • inflammatory muscle

• meningoencephalitis• Severe form EV-D68 in 2014 with deaths from severe respiratory

disease

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Zika

• Recent attention to the virus• Flavivirus• Interesting neurologic complications and prolonged survival in semen

Page 9: Rhabdovirus - smbs.buffalo.edu · Rhabdovirus • Nearly 100% fatal after symptoms appear • Bullet shaped virion • Helical nucleocapsid • Zoonotic • Glycoprotein Binds to

History

• Discovery in 1947 Zika Forest, Uganda• In 2007 febrile illness on the Yap Islands in the Federated States of

Micronesia• 2014 ZIKV Pacific Islands• 2015 ZIKV was identified for the first time in Brazil.

Page 10: Rhabdovirus - smbs.buffalo.edu · Rhabdovirus • Nearly 100% fatal after symptoms appear • Bullet shaped virion • Helical nucleocapsid • Zoonotic • Glycoprotein Binds to

MMWR

• Many infants had excessive, redundant scalp skin

• Arthrogryposis (contractures of extremities)• CT scans of infants brain

• Widespread brain calcifications• Lissencephaly, Pachygyria

• All 35 infants tested negative for syphilis, toxoplasma, CMV,

• Rubella and HSV

Borrowed from Dr. Parameswaran

Page 11: Rhabdovirus - smbs.buffalo.edu · Rhabdovirus • Nearly 100% fatal after symptoms appear • Bullet shaped virion • Helical nucleocapsid • Zoonotic • Glycoprotein Binds to

First case of microcephaly in infant related to Zika in Hawaii, Feb 2016

Borrowed from Dr. Parameswaran

Page 12: Rhabdovirus - smbs.buffalo.edu · Rhabdovirus • Nearly 100% fatal after symptoms appear • Bullet shaped virion • Helical nucleocapsid • Zoonotic • Glycoprotein Binds to

Zika Symptoms

• Fever• Maculopapular rash• Arthralgia• Non-purulent conjunctivitis• Travel

Page 13: Rhabdovirus - smbs.buffalo.edu · Rhabdovirus • Nearly 100% fatal after symptoms appear • Bullet shaped virion • Helical nucleocapsid • Zoonotic • Glycoprotein Binds to
Page 14: Rhabdovirus - smbs.buffalo.edu · Rhabdovirus • Nearly 100% fatal after symptoms appear • Bullet shaped virion • Helical nucleocapsid • Zoonotic • Glycoprotein Binds to

Guillain-Barre syndrome and Zika virus

• Higher than usual numbers of patients with Guillain-Barre syndrome noted in French Polynesia during Zika virus outbreak

• The first case had evidence for infection with Zika and Dengue• Reports of increase in numbers of GBS from six countries

recently in conjunction with Zika virus outbreaks• Recent report of GBS with Chikungunya outbreak from French

Polynesia

Borrowed from Dr. Parameswaran

Page 15: Rhabdovirus - smbs.buffalo.edu · Rhabdovirus • Nearly 100% fatal after symptoms appear • Bullet shaped virion • Helical nucleocapsid • Zoonotic • Glycoprotein Binds to

HSV 1 and 2

• Cold sores• Genital Lesions• Use to be able to predict on anatomy, not any more• Viral infection in most cells results in lysis and death

DS DNA

Page 16: Rhabdovirus - smbs.buffalo.edu · Rhabdovirus • Nearly 100% fatal after symptoms appear • Bullet shaped virion • Helical nucleocapsid • Zoonotic • Glycoprotein Binds to

Pathogenesis

• HSV infects some neuronal cells• These cell do not die but are maintained in a repressed state called

latency• Virus can then become activated but does not damage the neuron• Release of virions from neuron follows a complex process of

anterograde transport down the length of neuronal axons• Virus then enters epithelial cells and is called reactivation

Page 17: Rhabdovirus - smbs.buffalo.edu · Rhabdovirus • Nearly 100% fatal after symptoms appear • Bullet shaped virion • Helical nucleocapsid • Zoonotic • Glycoprotein Binds to
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Classical HSV

Page 19: Rhabdovirus - smbs.buffalo.edu · Rhabdovirus • Nearly 100% fatal after symptoms appear • Bullet shaped virion • Helical nucleocapsid • Zoonotic • Glycoprotein Binds to

Cardinal Findings of HSV

• Painful erythematous vesicles (blisters) on an erythematous base• Clustered in appearance• Depending on the immune status of the host, the lesions can be

locally invasive• Dew drops on rose petals

Page 20: Rhabdovirus - smbs.buffalo.edu · Rhabdovirus • Nearly 100% fatal after symptoms appear • Bullet shaped virion • Helical nucleocapsid • Zoonotic • Glycoprotein Binds to

Cold sore

Page 21: Rhabdovirus - smbs.buffalo.edu · Rhabdovirus • Nearly 100% fatal after symptoms appear • Bullet shaped virion • Helical nucleocapsid • Zoonotic • Glycoprotein Binds to

Orofacial

Page 22: Rhabdovirus - smbs.buffalo.edu · Rhabdovirus • Nearly 100% fatal after symptoms appear • Bullet shaped virion • Helical nucleocapsid • Zoonotic • Glycoprotein Binds to

Orofacial HSV

Page 23: Rhabdovirus - smbs.buffalo.edu · Rhabdovirus • Nearly 100% fatal after symptoms appear • Bullet shaped virion • Helical nucleocapsid • Zoonotic • Glycoprotein Binds to

Genital

Page 24: Rhabdovirus - smbs.buffalo.edu · Rhabdovirus • Nearly 100% fatal after symptoms appear • Bullet shaped virion • Helical nucleocapsid • Zoonotic • Glycoprotein Binds to

Genital

Page 25: Rhabdovirus - smbs.buffalo.edu · Rhabdovirus • Nearly 100% fatal after symptoms appear • Bullet shaped virion • Helical nucleocapsid • Zoonotic • Glycoprotein Binds to

Genital

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Genital Disease

• First episode is generally the worst• Treatment of the primary infection has NO effect on rate of

recurrence• Women have higher incidence of developing herpes meningitis with

primary infection• Can prevent infection in discordant couples with daily suppression of

the infected partner• Prophylaxis for individual generally not recommended unless 6 or

more episodes in a 6 month period

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Other Manifestations

• Aseptic meningitis• Mollaret’s meningitis• Herpetic Whitlow• Herpes Simplex Encephalitis• Herpes gladiatorum• HSV keratitis• Neonatal Herpes• Herpes in pregnancy• HSV in HIV

Page 28: Rhabdovirus - smbs.buffalo.edu · Rhabdovirus • Nearly 100% fatal after symptoms appear • Bullet shaped virion • Helical nucleocapsid • Zoonotic • Glycoprotein Binds to

Herpetic Whitlow

Page 29: Rhabdovirus - smbs.buffalo.edu · Rhabdovirus • Nearly 100% fatal after symptoms appear • Bullet shaped virion • Helical nucleocapsid • Zoonotic • Glycoprotein Binds to

Keratitis

Page 30: Rhabdovirus - smbs.buffalo.edu · Rhabdovirus • Nearly 100% fatal after symptoms appear • Bullet shaped virion • Helical nucleocapsid • Zoonotic • Glycoprotein Binds to

HSV Encephalitis

Page 31: Rhabdovirus - smbs.buffalo.edu · Rhabdovirus • Nearly 100% fatal after symptoms appear • Bullet shaped virion • Helical nucleocapsid • Zoonotic • Glycoprotein Binds to

Diagnosis and Treatment - HSV• Diagnosis

• Mainly clinical• Tzanck smear sometime helpful

• Multinucleated giant cells• Intra-nuclear inclusion

• HSV viral culture or PCR• Serology only useful in sero-

epidemiologic circumstances but could document primary infection. Need to know about IgM and IgG

• Treatment• Acyclovir and congeners• Mechanism in next lecture

Page 32: Rhabdovirus - smbs.buffalo.edu · Rhabdovirus • Nearly 100% fatal after symptoms appear • Bullet shaped virion • Helical nucleocapsid • Zoonotic • Glycoprotein Binds to

Varicella-Zoster

• Causes both chickenpox (childhood disease) and shingles• Chickenpox

• Generally mild disease but may have major complication• Fewer than 2 deaths/100,000 cases

• MUCH worse disease with complication in adults• Over 30 deaths/100,000 cases• Most from pneumonia

DS DNA

Page 33: Rhabdovirus - smbs.buffalo.edu · Rhabdovirus • Nearly 100% fatal after symptoms appear • Bullet shaped virion • Helical nucleocapsid • Zoonotic • Glycoprotein Binds to

Chickenpox

• Prodrome may occur 1 to 2 days before the onset of rash• Lassitude and fever to 103˚F• Malaise, pruritus, anorexia, and listlessness• Skin manifestations

• Maculopapules, vesicles, and scabs in varying stages of evolution• Clear vesicular fluid then pustulate and scab

• “Dewdrop-like” early - rapidly become purulent

• Small 5 mm-13 mm• Central umbilication occurs as healing progresses. • First trunk and face then centrifugally• The hallmark of the infection is the appearance of lesions at all stages

Page 34: Rhabdovirus - smbs.buffalo.edu · Rhabdovirus • Nearly 100% fatal after symptoms appear • Bullet shaped virion • Helical nucleocapsid • Zoonotic • Glycoprotein Binds to

Chickenpox

Page 35: Rhabdovirus - smbs.buffalo.edu · Rhabdovirus • Nearly 100% fatal after symptoms appear • Bullet shaped virion • Helical nucleocapsid • Zoonotic • Glycoprotein Binds to

Chickenpox Complications

• CNS disease• Herpes Zoster opthalmicus• Pneumonia

• 1/400 adults• Military study showed 16% of recruits had CXR abnormalities

• Only ¼ of those had cough• Only 10% had pulmonary sx to go with CXR

• Reyes syndrome with concomitant aspirin

Page 36: Rhabdovirus - smbs.buffalo.edu · Rhabdovirus • Nearly 100% fatal after symptoms appear • Bullet shaped virion • Helical nucleocapsid • Zoonotic • Glycoprotein Binds to

Zoster

• Shingles• Reactivation of prior infection

Page 37: Rhabdovirus - smbs.buffalo.edu · Rhabdovirus • Nearly 100% fatal after symptoms appear • Bullet shaped virion • Helical nucleocapsid • Zoonotic • Glycoprotein Binds to

Zoster

Page 38: Rhabdovirus - smbs.buffalo.edu · Rhabdovirus • Nearly 100% fatal after symptoms appear • Bullet shaped virion • Helical nucleocapsid • Zoonotic • Glycoprotein Binds to

Herpes Zoster Opthalmicus

Page 39: Rhabdovirus - smbs.buffalo.edu · Rhabdovirus • Nearly 100% fatal after symptoms appear • Bullet shaped virion • Helical nucleocapsid • Zoonotic • Glycoprotein Binds to

Diagnosis and Treatment - Zoster• Diagnosis

• Mainly clinical• Tzanck smear sometime

helpful• Multinucleated giant cells• Intra-nuclear inclusion

• VZV viral culture or PCR• Culture much more “finicky”

than HSV culture

• Treatment• Acyclovir and congeners• Mechanism in next lecture

Page 40: Rhabdovirus - smbs.buffalo.edu · Rhabdovirus • Nearly 100% fatal after symptoms appear • Bullet shaped virion • Helical nucleocapsid • Zoonotic • Glycoprotein Binds to

Varicella-Zoster

• Prevention• Vaccine

• Live-attenuated virus• NOT used in immunocompromised individuals or with those people in the same

household• Lower dose in childhood• Higher dose in adult to prevent zoster

• Treatment• Higher dose acyclovir