Rhabdovirus,

Filovirus, Bornavirus
Rhabdoviruses

FILOviruses (NOT Flav)

Marburgvirus

BORNaviridae (NOT Buny)

Ebolavirus

Bornavirus

Rod or bullet shaped*****

Enveloped
Envelope/Shape Glycoprotein peplomers (surround the nucleocapsid)
-These are what give bullet shape
-Contain neutralizing epitopes
-Are target for immune prophylaxis & immunotherapy

Enveloped

Enveloped
**(replicates in host nucleus= unusual)**

(-) ssRNA

(-) ssRNA

(-) ssRNA
5 viral proteins encoded

DNA/RNA
[Worldwide]

[Endemic to AFRICA]

[Endemic to Sub-Saharan AFRICA]

[Central Europe, N. America, & Asia]

-Usually via bite from infected animal (virus in saliva)

--> Domestic animals: dogs, cats, cattle (rare d/t vaccinations)
--> Wild animals:

Source/reservoir:
-not really known
-maybe bats & wild monkeys

Source/reservoir:
-most likely zoonotic

-Infects mammals & birds

Transmission:
-Direct contact w/ infected animals or humans
-Contact w/ infected tissue/blood/secretions

-Human infections assoc. w/ outbreaks in

Transmission:
horses
-Direct contact w/ infected animals or
humans
-Contact w/ infected tissue/blood/secretions

Risk:
-working with wild primates
-BSL-4 lab personnel

Transmission
-Exposure to mucus membranes (eyes, nose, mouth)
-Possibly inhalation of aerosols in caves with infected bats
-Corneal transplantation

Replication initially in muscle/NON-nervous tissue @ bite site

--> or, immediate entry into CNS based on some models

Pathophys

1. Replicates in monocytes, macrophages,

dendritic cells, and others

Glycoproteins [impt virulence factors]

Soluble glycoprotein (sGP)

Prodrome:
2. Cytokine storm of proinflammatory cytokines d/t -secreted, binds neutrophils, and block Ab
--> Infects peripheral nerves --> spreads to CNS via RETROgrade axonal transport replication in monocytes
action
--> both sensory & motor fibers involved
-not found in Marburgvirus
3. Tissue necrosis in parenchymal cells of liver,
-Spreads within CNS via intra-axonal
spleen, lungs, lymph nodes
Surface (GP)
--> may move from CNS via ANTEROgrade (found in motor, sensory, & autonomic
- transmembrane/ envelope, binds
fibers)
4. Break down of vascular endothelial cell
endothelial cells
(hemorrhaging)
Neurological phase: infection of brain
-Evidence for replication in blood during
early/aSx infection
-Replication in ganglia, spreads to glands, skin, salivary glands
-Rapid dissemination to all tissues
-Invasion, replication, & destruction of
Sneaky little devil: Won't get immune response until late in disease when virus goes
endothelial cells
from CNS to other organs (remember CNS is protected from immune system)
-Disseminated intravascular coagulation
-Widespread & severe focal necrosis
--> most severe in liver
-Hemorrhagic manifestations

-Neurotropic, spreads through CNS

-Infects parenchymal cells of diff. organs &
peripheral blood mononuclear cells
-Not cytolytic
-Persistent infection
T-cell is what control infection, but also
causes tissue damage
-Immune modulated damage

Incubation: Asymptomatic
-Long pre-clinical period (4 days - 19 years)
--> dep. upon proximity of infection site to CNS/brain
--> humans > 6 years
-Low titer [virus in muscle]
Prodrome: (2-10 days)
-Bite site or involved limb:
--> Pain, Pruritus, Paresthesia (tingling, tickling, itching)
-Other symptoms:
--> Fever, HA, N/V, anorexia, lethargy/ malaise
-Low titer [virus in CNS & brain]
Disease

Neurological period: (2-7 days) CNS involvement

-Furious
--> hyperactive, bizarre behavior, anxiety, hallucinations, then periods of calm)
-Paralytic
--> paralysis (20%), hydrophobia, nuchal rigidity, pharyngeal spasms, paresis
--> some only have paralytic sx
-HIGH titer [virus in brain &other sites]
Coma: (0-14 days)
-Hypoventilation, Hypotension
-Secondary infections
-Cardiac arests
-HIGH titer [virus in brain &other sites]
Negri bodies:
-intracytoplasmic inclusion bodies of nucleocapsids
-found in neurons
[once hallmark, no longer used]

-Causes viral hemorrhagic fever

Incubation: 5-10 days
-Sudden onset of Flu- like symptoms @ first
-After 5 days of onset of sx:
--> Maculopapular rash on chest, back, &
stomach
-Severity of symptoms increases
-Additional sx:
--> Jaundice, pancreas inflammation, severe
weight loss, delirium, shock, liver failure
--> Massive hemorrhaging****, multisystem
failure
-DEATH (25%)

Neuropsychiatric disorders*******
Schizophrenia
Autism
Other neuopsych dz

Incubation: 3-21 days

-Early (abrupt) onset of flu-like symptoms

-Presence of viral Ab &/or peripheral blood

mononuclear cells

-Followed by:
--> Diarrhea, vomiting, stomach pain,
conjunctivitis, dysphagia
--> Hemorrhaging from GIT, mucus
membranes, puncture sites
--> cutaneous rash
-In FATAL cases:
--> Obtund
--> Tachypnea, hiccups
--> SHOCK

If they survive:
Orchitis, hepatitis
Recurrent or prolonged hepatitis
Transverse myelitis/evetis
Inflammation of testes, spinal cord, parotid gland

Serology, PCR, viral cx by CDC

Need to be extremely careful handling samples
(BSL-4)

Samples & Methods (Antemortem)

[Early sx]:
-Detect virus in blood/tissues via ELISA or
PCR
[Survivors]:
Serology

RT-PCR
--> peripheral blood mononuclear cells
Serology

[Fatal cases]:
Immunohistology of tissues, virus isolation,
PCR

***Saliva:*** [preferred & easiest]

[NO tracheal aspirates or sputum!!!]
-RT-PCR
-Extracted nucleic acid ID
-Isolation of virus (specialized labs, only when other tests are inconclusive)

Diagnosis

-Causes viral hemorrhagic fever

--> more severe vs. Marburgvirus
--> 90% fatality rate

Need to be extremely careful handling

samples (BSL-4)

Neck biopsy
-Posterior region of neck @ hairline, should be of size & depth to incl. 10 hair follicles w/
cutaneous nerves at base of follicle
-RT- PCR or direct (testing for Ag) immunoflorescent stain
Serum & CSF
-Indirect (testing for Ab) immunofluorescent stain
-Virus neutralization
Brain Bx [unwarranted unless bx (-) for herpes encephalitis]
-RT-PCR-Indirect (testing for Ab) immunofluorescent stain
-Indirect (testing for Ag) immunofluorescent stain
Samples & Methods (Postmortem) [rarely done]
-consult State Dept
-Sample: CSF (brain)

Treatment

Dx usually late in dz process.

Supportive Care

Supportive Care

No specific tx.

-Replace fluids/electrolytes
-Replace blood & clotting factors
-Transfusion of FFP

-Replace fluids/electrolytes

Supportive care
[Rapid or suspected rabid domestic dog or cat&
Wild animal bites]:
RIG & HDCV/PCEC vaccine

Vaccine: HDCV or PCECV

Prevention

[Domestic animals]
-vaccination
-restriction of movement
-animal control programs
[Wildlife]
-population control ineff.
-vaccination programs

-Controversial: Heparin

Secondary exposure: barrier nursing techniques

Ribavirin