Reorhabdogit

FE A. BARTOLOME, MD, FPASMAPDepartment of Microbiology &

ParasitologyOur Lady of Fatima University

Reovirus, Rhabdovirus andReovirus, Rhabdovirus andGastrointestinal VirusesGastrointestinal Viruses

Reoviridae

respiratory and enteric viruses not associated with any known disease process Respiratory, Enteric, Orphan

Members:

1. Orthoreovirus – mild URT illness, GIT illness, biliary atresia

2. Orbivirus/Coltivirus – febrile illness associated with headache and myalgia (zoonosis)

3. Rotavirus – GIT illness, respiratory tract illness (?)

Non-enveloped; double-layered protein capsids with dsRNA genomes (“double:double”)

Stable over wide pH & temperature changes & in airborne aerosols

ReoviridaeReoviridae

STRUCTURE:

Icosahedral with double stranded segmented genome

Reovirus – 10 segments

Rotavirus – 11 segments

(+) re-assortment of gene segments create hybrid viruses

ReoviridaeREPLICATION:

Ingestion

Proteolytic cleavage of outer capsid in GIT

Formation of intermediate/infectious viral particle (ISVP)

ISVP release core into cytoplasm

Enzymes in core initiate mRNA production using + strand as template

Reoviridae

REPLICATION:

Occurs in the cytoplasm

dsRNA remains in the core

Virus leaves the cell during cell lysis

Mammalian reovirus

Ubiquitous present in sewage & river water

3 serotypes (1, 2 & 3) based on neutralization and hemagglutination-inhibition tests

Most people infected during childhood (+) antibodies in 75% of adults

Reoviridae: Orthoreovirus

PATHOGENESIS & IMMUNITY

No significant disease in humans

After ingestion & proteolytic production of ISVP, binds to M cells in small intestines transfer virus to lymphoid tissue of Peyer’s patches replicate (+) viremia

(+) humoral & cellular immune response to outer capsid protein


CLINICAL SYNDROMES:

1. Usually asymptomatic

2. Common cold-like mild upper respiratory tract illness

3. Gastrointestinal disease

4. Biliary atresia

LABORATORY DIAGNOSIS:

1. Assay of viral antigen or RNA in clinical material

2. Virus isolation

3. Serologic assays


A 6-month-old boy was seen in the emergency room after two days of persistent watery diarrhea and vomiting accompanied by a low-grade fever and mild cough. The infant appeared dehydrated and required hospitalization.

Rota “wheel”

One of the most common agents of infantile diarrhea worldwide

Ubiquitous worldwide

95% of children infected by 3 – 5 years old

Stable at: room temperature, treatment with detergents, pH 3.5 – 10, repeated freezing & thawing; survives on fomites

Divided into:

1. Serotypes – based primarily on VP7 outer capsid protein

2. Groups – based on antigenicity of VP6 & electrophoretic mobility of genomic segments A to G group A causes human disease

Reoviridae: Rotavirus

PATHOGENESIS:

• MOT: fecal-oral, possibly respiratory route

• Adsorption to columnar epithelial cells covering villi of SI release of NSP4 protein (+) cytolytic & toxin-like activity loss of electrolytes & prevention of water re-absorption watery diarrhea severe dehydration


NSP4 protein promotes:1. calcium influx into enterocytes2. release of neuronal activators3. neuronal alteration in water absorption

Shortening and blunting of microvilli; mononuclear cell infiltration into lamina propia

1010 viral particles/gm of stool released during disease maximal shedding 2 – 5 days after start of diarrhea

(+) outbreaks in pre-schools and daycare centers


CLINICAL SYNDROMES:

• I.P. = 48 hrs

• self-limited

• vomiting, diarrhea, fever, dehydration

• (-) fecal leukocytes and blood

• may be fatal in infants from developing countries & who are malnourished and dehydrated before the infection



1. direct detection of viral antigens in stool – method of choice

2. enzyme immunoassay

3. latex agglutination

4. serology – four fold increase in antibody titer


A 24-year old mountaineering student developed fever, chills, and headache 4 days after hiking in the forest. He also complained of photophobia, muscle pain, joint pains and lethargy. P.E. showed redness of conjunctiva, (+) LAD, and palpable liver margins. Maculopapular rashes were noted. Laboratory exam revealed leukopenia with neutropenia and lymphopenia. He remembers being bitten by an insect during the hike.

Reoviridae: Coltivirus & Orbivirus

features different from other Reoviridae:

1. Orbivirus – outer capsid without discernible capsomeric structure; inner capsid icosahedral

2. Causes viremia – long lasting

3. Infects erythrocyte precursors without damaging them remains within the cells protected from immune response (+) viremia


Coltivirus:

causes Colorado Tick Fever vector: Dermacentor andersoni (wood tick) one of the most common tick-borne diseases in the U.S. symptoms of acute disease resemble dengue infect vascular endothelial & vascular smooth muscle cells & pericytes weak capillary structure (+) hemorrhage hypotension shock neuronal infection – meningitis & encephalitis (+) leukopenia involving both neutrophils and lymphocytes HALLMARK


LABORATORY:

Immunofluorescence – most rapid and best technique detection of viral antigen on surface of red blood cells on blood smear

Antibody titer – specific IgM (+) 45 days after onset of illness presumptive evidence of acute or very recent infection

Other Gastrointestinal Viruses

CALICIVIRUSES

5 groups:1. Norwalk 4. Marine virus2. Sapporo viruses 5. Rabbit hemorrhagic dse virus3. Hepatitis E

approx. same size as Picornaviruses naked, positive sense ssRNA viruses viruses distinguishable by capsid morphology compromise function of intestinal brush border

prevent re-absorption of water and nutrients cause outbreaks of gastroenteritis


I.P. = 24 – 48 hrs MOT: 1. fecal-oral – water, shellfish, food service

2. possible airborne

Immunity short-lived & not protective

Symptoms similar to Rotavirus infection- Norwalk & related viruses diarrhea, n & v, esp. in children; fever in 1/3 of patients

Resolve within 12 – 60 hrs


ASTROVIRUSES seen in stools from infants & young children with

diarrhea

may be shed in extraordinarily large amounts in feces

associated with diarrhea in young children in daycare centers

symptoms similar to Norwalk but without vomiting

minimally pathogenic


ADENOVIRUS Replicates in intestinal cells

Adenovirus group F serotypes 40 & 41 infantile gastroenteritis detected by electron microscopy or antigen-based assays

Usually sub-clinical

An 11-year old boy was brought to the hospital after falling. His bruises were treated and he was released afterwards. The following day, he refused to drink water with his medicine, and he became more anxious. That night, he began to act up and hallucinate. He was also salivating and had difficulty breathing. Two days later, he had high grade fever and experienced two episodes of cardiac arrest. His condition continued to deteriorate, and he died 11 days later. When the parents were questioned, it was learned that the boy had been bitten on the finger by a dog 6 months earlier.

Rhabdovirus

“rhabdo” rod

bullet-shaped; enveloped; icosahedral nucleocapsid

negative ssRNA prototype for replication of negative stranded enveloped viruses

Rhabdovirus

• encode 5 proteins:1. G – synthesized by membrane-bound

ribosomes; attach to host cell & internalized by endocytosis; generates neutralizing antibodies; prototype for studying eukaryotic glycoprotein processing

2. N – major structural protein; protects the RNA from ribonuclease digestion

3. L and NS – constitute the RNA-dependent RNA pol

4. M – matrix protein; lies between envelope & nucleocapsid

Rhabdovirus

RABIES VIRUS

most significant pathogen

reservoir: wild and domestic animals

source of virus:1. Major – saliva in bite of rabid animal2. Minor – aerosols in bat caves containing

rabid bats

found worldwide; no seasonal incidence

Rhabdovirus

PATHOGENESIS & IMMUNITY

• MOT: 1. bite of rabid animal 2. inhalation of aerosolized virus 3. transplanted infected tissue (e.g. cornea) 4. inoculation through intact mucosal membrane

• rabies infection of animal cause secretion of the virus in the animal’s saliva & promotes aggressive behavior “mad dog” promote transmission

• not very cytolytic remains cell associated

RhabdovirusMOT

Bind to nicotinic Ach or ganglioside receptors of neurons

Muscle at site of inoculation

Replicate at site of bite

Skin of head & neck, salivary glands, retina, cornea, nasal mucosa, adrenal

medulla, renal parenchyma, pancreatic acinar cells

Wks to mosWks to mos

Afferent neuronsAfferent neurons

CNS (hippocampus, brainstem, ganglionic cells of pontine nuclei,

Purkinje cells of cerebellum)

Incubation phaseIncubation phase

Travel by retrograde axoplasmic transport to DRG & to SC

Prodrome phaseProdrome phase

Neurologic phaseNeurologic phase

Rhabdovirus

• length of incubation period determined by:1. concentration of virus in inoculum2. proximity of wound to brain3. severity of the wound4. host’s age5. host’s immune status

• rarely causes inflammatory lesions• CMI with little or no role in protection• antibody can block spread of virus to CNS if

administered or generated during the incubation period

• long incubation period allows active immunization as post-exposure treatment

Rhabdovirus PROGRESSION OF RABIES DISEASE

Disease Phase

Symptoms Time (days)

Viral Status Immunologic status

Incubation Asymptomatic 60 – 365 after bite

Low titer, virus in muscle

Prodrome Fever, n & v, anorexia, headache, lethargy, pain at bite site

2 – 10

Low titer, virus in CNS and brain

Neurologic Hydrophobia, pharyngeal spasms, hyperactivity, anxiety, depression

CNS: loss of coordination, paralysis, confusion

2 – 7 High titer, virus in brain and other sites

Detectable antibody in serum & CNS

Coma Coma: cardiac arrest, hypotension, hypoventilation, secondary infections

0 – 14 High titer, virus in brain and other sites

Death

Rhabdovirus


• done to confirm the diagnosis

1. detection of viral antigen in CNS or skin via immunofluorescence most widely used

2. virus isolation – cell culture 3. serology – antibody titers in serum and CSF 4. detection of Negri bodies – intracytoplasmic

inclusions containing aggregates of viral nucleocapsids in affected neurons HALLMARK

Rhabdovirus

PRE-EXPOSURE VACCINATION:• HDCV IM or intradermally x 3 doses 2 years

protection

POST-EXPOSURE PROPHYLAXIS:1. local treatment of wound – wash immediately with soap

& water2. WHO Expert Committee on Rabies – instillation of anti-

rabies around the wound3. active + passive immunization

• HDCV IM on day of exposure then on days 3, 7, 14 & 28 + 1 dose human rabies immune globulin (HRIG)

Reorhabdogit

Health & Medicine

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