Module 1.

8
RNA Viruses
 • Most are single stranded, enveloped,
RNA Viruses show helical capsid symmetry, and
replicate in the cytoplasm.
EXCEPTIONS:
• Arenaviridae • Filoviridae 1. Reoviridae are double stranded
• Astroviridae • Orthomyxoviridae 2. Three are nonenveloped:
• Caliciviridae • Paramyxoviridae Picorna, Calici, Reoviridae
• Coronaviridae • Picornaviridiae 3. Five have icosahedral symmetry
• Bunyaviridae • Reoviridae Reo, Flavi, Picorna, Calici, Toga

• Flaviviridae • Retroviridae * Rhabdo has helical symmetry but shaped

like a bullet
• Togaviridae • Rhabdoviridae
4. Two undergo replication in the nucleus:
Retro, Orthomyxo
Astroviridae
• Astroviruses are unsegmented, positive-sense
RNA viruses
• They were first discovered in 1975 using electron
microscopes following an outbreak of diarrhea in
humans.
• They cause diarrheal illness (gastroenteritis) where
infants and young children are most likely to have the
diarrhea.
What are the Arenaviridae?
• Arenaviridae
* A family of viruses whose members are generally associated
with rodent-transmitted disease in humans.
• family of negative , single-stranded, enveloped RNA viruses.
Taxonomy
• Family: Arenaviridae
• Genus: Arenavirus
• Subgroup (2):
A) LCM-LASV Complex (Old World
Arenaviruses)
B) Tacaribe Complex (New World
Arenaviruses)
Virus Morphology
• Spherical
• An average diameter of 110-130 nm
• Enveloped in a lipid membrane.
• Has grainy particles that are ribosomes
acquired from their host cells. (derived from
the Latin "arena," which means "sandy." )
• Their genome is composed of RNA only.
• New viral particles, called virions, are
created by budding from the surface of their
hosts’ cells.
Pathogenesis
• Chronic infection in rodent host.
(However, the viruses do not appear to cause obvious illness in them.)

• Rodents that carry the Old World arenaviruses can transmit the virus from
mother to offspring during pregnancy. Thus, virus remains in the rodent
population generation after generation
• New World arenavirus carrying rodents can only transmit among adult
rodents, so only a portion of mice are infected at one time. This leads to
cyclic trends in the incidence of human cases.

• Human infection occurs by contact with rodent excretions

• Contaminated food
• Dust with urine (inhale)
• Exposed wounds

• Secondary spread (person-person)

• Nosocomial
• Contact with infected blood and other excretions
• Contact with contaminated medical equipment
Symptoms
• The onset of the hemorrhagic fevers caused by
Lassa, Junin, Machupo, and Guanarito viruses:
- within 7 to 14 days,
-pyrexia
-headache
-sore throat
-myalgia

Virus can be recovered from the blood and serum for

up to 3 weeks after onset of the infection.

Lassa virus can be recovered from the urine for up to

5 weeks.
Filoviridae
• The family Filoviridae is the taxonomic home of
several related viruses that form filamentous
infectious viral particles, and encode their genome
in the form of single-stranded negative-sense RNA.
• Scientific name: Filoviridae
• Rank: Family
• Higher classification: Mononegavirales
• Lower classifications: Ebolavirus, Marburg virus
• These agents cause severe or fatal hemorrhagic
fevers and are endemic in Africa.
Filoviruses (Filoviridae)
• These viruses may be endemic in bats or wild
monkeys and can be spread to humans and
between humans.
• Contact with the animal reservoir or direct
contact with infected blood or secretions
can spread the disease.
• These viruses have been transmitted by
accidental injection and through the use of
contaminated syringes.
• Health care workers tending the sick and
monkey handlers may be at risk.
Arboviruses
• Are transmitted by arthropods.
• Occur in several taxonomic families:
• Bunyaviruses
• California encephalitis group (La Crosse virus); Rift Valley fever
• Transmitted by mosquitoes, ticks, and sandflies
• Hantaviruses
• Flaviviruses
• Yellow fever, dengue fever, West Nile virus, Japanese encephalitis, and St. Louis
encephalitis virus
• Transmitted by mosquitoes
• Togaviridae family
• Rubivirus causes rubella (German measles/3-day measles)
• Alphaviruses
• Eastern, Western, and Venezuelan equine encephalitis
• Chikungunya virus – transmitted by Aedes mosquitoes with initial symptoms of fever, rash and
joint pain/swelling.
11
• Transmitted by mosquitoes Copyright © 2014, by Mosby, an imprint of Elsevier Inc.
Bunyaviridae

Genus Disease(s)
Bunyavirus LaCrosse encephalitis
Phlebovirus Rift Valley Fever
Nairovirus Crimean-Congo Hemorrhagic Fever
Tospovirus Plant Virus
Hantavirus Hemorrhagic Fever with Renal
Syndrome
Hantavirus Pulmonary Syndrome
Hantavirus (Bunyaviridae)
• Rodent-borne
• Transmitted through inhalation of rodent excreta
• Hanta pulmonary syndrome:
• Symptoms:
• After 11 to 32 days, symptoms are headache, fever, and body aches.
• Symptoms progress to hemorrhagic fever, kidney disease, and acute respiratory failure.
• Strains of hantaviruses include:
• Sin Nombre virus—Transmitted by deer mice
• Bayou virus—Transmitted by the rice rat
• Black Creek Canal virus—Transmitted by the cotton rat
• New York–type 1 virus—Transmitted by the white-footed mouse

Copyright © 2014, by Mosby, an imprint of Elsevier Inc. 13

Hepatitis C (Flaviviridae)
• Enveloped, icosahedral capsid
• Is transmitted parenterally or sexually.
• Diseases
• Acute and chronic hepatitis
• Hepatocellular carcinoma
• Diagnosis
• Serologic testing
• Real-time polymerase chain reaction (RT-PCR)
• Viral genotyping
• Treatment
• Interferons Copyright © 2014, by Mosby, an imprint of Elsevier Inc. 14
Hepatitis C (cont’d)

Copyright © 2014, by Mosby, an imprint of Elsevier Inc. 15

 Coronaviridae
Family Coronaviridae • The family Coronaviridae Includes genera
Torovirus and Coronavirus (CoV)
Common name Coronaviruses
• RNA viruses with a crown-like appearance
Virus Coronavirus
• Pleomorphic, roughly spherical, medium-sized,
Morphology • Positive (+) Single-stranded RNA
• Non-segmented
enveloped RNA viruses.
• Helical symmetry • CoV is once considered a harmless virus
• Enveloped capable of causing human “cold”
• Replication in the cytoplasm,
Transmission Direct contact or aerosol (Bailey &Scott’s)
• CoVs cause a wide variety of disease in
animals and birds.
Disease • Upper respiratory tract infection (common cold)
• Gastroenteritis especially in children
• SARS ❖ The prefix corona- results from the viral
Diagnosis Electron Microscopy, RT-PCR structure and the crownlike surface projections
on the external surface of the virus that can be
Treatment Supportive (Bailey &Scott’s)
seen with electron microscopy.
Prevention Avoid contact with virus (Bailey &Scott’s)
Coronaviridae
1. Severe Acute Respiratory Syndrome(SARS)
is a viral respiratory disease of zoonotic origin caused by the SARS coronavirus (SARS-
CoV). Between November 2002 and July 2003, an outbreak of SARS in southern China
caused an eventual 8,098 cases, resulting in 774 deaths reported in 37 countries, with the
majority of cases in Hong Kong (9.6% fatality rate) according to the World Health
Organization
➢ can be spread by respiratory droplets produced through sneezing and coughing
➢ Also transmitted through touching contaminated surfaces or objects
➢ Symptoms: Rapid onset fever, Dry cough, Dyspnea, Headache, Myalgia, Malaise
Coronaviridae
• Human respiratory coronaviruses causes colds and occasionally pneumonia in adults.
• Together with rhinoviruses and coronaviruses cause more than 55% of the “COMMON
COLDS” in human population.
• CoVs also are thought to cause diarrhea in infants based on the presence of coronavirus-
like particles in the stool of symptomatic patients (seen in electron microscope).

• Diagnostic methods:
1. Electron microscope- detects coronavirus-like particles in the stool of patients (commonly
children) with gastroenteritis.
2. RT-PCR – sensitive and specific diagnostic method, recommended method for laboratory
diagnosis.
Picornavirus
• picornaviruses are named for their small (“pico” + “RNA” = picorna) size,
they include a large and diverse array of viruses – over 200 serotypes.
• The family PICORNAVIRIDAE comprises five genera, namely,
enteroviruses, rhinoviruses, hepatoviruses, cardioviruses, and
aphthoviruses.
• The picornaviruses are small (22 to 30 nm) nonenveloped, single-
stranded RNA viruses with cubic symmetry.
• The virus capsid is composed of 60 protein subunits, each consisting of
four poly-peptides VP1–VP4. Because they contain no essential lipids,
they are ether resistant.
Picornavirus
• They replicate in the cytoplasm.
• The picornaviruses that affect humans are the enteroviruses, found
primarily in the gut; the rhinoviruses, found in the upper respiratory
tract and hepatovirus (Hepatitis A virus) in the intestine and liver.
Subclinical infections with the picornaviruses are common.
• Picornaviruses contain positive sense, single-stranded RNA that is
approximately 7-8 kilobases long.
• The genome is monopartite and polyadenylated at the 3’ end,
but has a VPg protein at the 5’ end in place of a cap.
Picornavirus
• The picornavirus virion is an
icosahedral, nonenveloped,
small (22 to 30 nm) particle. The
capsid proteins encase a sense
RNA strand consisting of
approximately 7,500
nucleotides.
• The RNA carries a covalently
bound noncapsid viral protein
(VPg) at its 5′ end and a
polyadenylated tail at its 3′ end.
Rhinovirus (Picornaviridae)
• Causes the “common cold.”
• Transmission:
• Self-inoculation through the eyes or nose
• Direct contact of aerosols
• Symptoms are watery nasal discharge, headache, malaise,
sneezing, nasal congestion, sore throat, and cough.
• Has over 100 serotypes
• Testing:
• Is not often required.
• Virus grows in MRC-5 cell lines at a reduced temperature (30ºC).
• Cytopathic effect (CPE) appears as large and small round refractile cells.

Copyright © 2014, by Mosby, an imprint of Elsevier Inc. 22

Orthomyxoviridae
• Spherical virions.
• At this virions’ center lie 8 segments of negative
stranded RNA put together with a protein
(nucleocapsid protein NP) into a helical
symmetry capsid. Surrounding the nucleocapsid
lies an outer membrane studded with long
glycoprotein spikes.
• Two types of glycoprotein:
1. Hemagglutinin Activity (HA)
2. Neuraminidase Activity (NA)
• Anchoring the bases of each of these spikes on
the inside of the viral lipid bilayer are membrane
proteins (M proteins)
Hemagglutinin (HA)
• Can attach to host sialic acid receptors.
• Sialic acid receptors are present on the
surface of erythrocytes, so viruses with HA
glycoproteins can cause heme-agglutination
when mixed with RBCs.
• HA binding to the sialic acid receptors
activates fusion of the hose cell membrane
with the virion membrane, resulting in the
dumping of the viral genome into the host
cell.
Neuraminidase (NA)

• An important component of mucin

• NA cleaves neuraminic acid and disrupts the
mucin barrier, exposing the sialic acid
binding sites beneath
• Antibodies against NA are also protective.
Paramyxoviridae
• Similar structures with orthomyxoviridae. The
difference are that:
1. The negative stranded RNA is in a single strand not
segmented.
2. The HA and NA glycoproteins are located in the same
spike, not 2 different spikes.
3. They possess a fusion protein, which is not present in the
orthomyxoviridae, this F protein causes an infected host to
fuse together into a multinucleated giant cell.
• Four types of paramyxoviridae that can
cause human disease.
1. Parainfluenza Virus
2. Respiratory syncytial virus
3. Mumps virus
4. Measles
Retroviruses
• Are single-stranded RNA.
• Contain reverse transcriptase (RT), which converts RNA to DNA.
• HIV—type 1 or 2:
• Infects cluster of differentiation 4 (CD4) T lymphocytes, monocytes, and cells
of the central nervous system (CNS).
• Causes acute influenza-like disease, acquired immunodeficiency syndrome
(AIDS), and malignancies.
• Is treated with multiple-drug therapy.
• HTLVs:
• Causes T-cell leukemia and lymphoma and tropical spastic paraparesis (HTLV–
type 1).
Copyright © 2014, by Mosby, an imprint of Elsevier Inc. 27
Untreated Human
Immunodeficiency Virus

Copyright © 2014, by Mosby, an imprint of Elsevier Inc. 28

Western Blot

Copyright © 2014, by Mosby, an imprint of Elsevier Inc. 29

Retroviridae
Retrovirus Virions
Thin Section EM of Some Retroviruses
Reovirus
◦ Cytoplasmic replication
◦ Extremely stable
 Heat resistant
 Remain infectious after treatment of pH 3-9

• Rotaviruses
 Major cause of diarrhea
 Similar to reoviruses in morphology and replication strategy
 Classification
◦ Five serological groups (A-E)
◦ Group A can be distinguished from others by electophoretic mobility of gene
segments
 Animal susceptibility
◦ Rotaviruses are highly promiscuous
◦ Major cause of disease in livestock industry
 Many young animals can become persistent carriers, shedding virus to other
animals
 Infect villi of small intestine
 Multiply in enterocytes
 Enterocytes are replaced by crypt cells = diarrhea ensues
Caliciviruses
▪ cause gastrointestinal infections.
 Gastroenteritis
◦ Norwalk virus and Norwalk-like viruses
◦ Recently infamous for cruise ship infections
◦ Extremely difficult to decontaminate
◦ Unculturable (propagated in animals)
Norovirus transmission Transmission:
• Fecal – oral:
• food
• water
• Contact:
▪ person – person
▪ environment– person
 RHABDOVİRİDAE
• Rhabdos (greek) rod
• Pathogens of mammals, birds, fish, plants
Rabies virus

Unique features of Rhabdoviruses

• Bullet-shaped
• Enveloped
• Negative, single-stranded RNA
• Prototype for (-) RNA viruses
• Replication in the cytoplasm
 Rabies virus/Disease Mechanisms

• Rabies is usually transmitted in saliva and is

acquired from the bite of a rabid animal
• Virus is not very cytolytic and seems to
remain cell-associated
• Virus replicates in the muscle at the site of
the bite with minimal or no symptoms
• The length of the incubation phase is
determined by the infectious dose and the
proximity of the infection site to the CNS and
brain
Rabies virus/Disease Mechanisms

• After weeks to months, the virus infects the

peripheral nerves and travels up the CNS to
the brain (prodrome phase)
• Infection of the brain causes classic
symptoms, coma, and death (neurologic
phase)
• During the neurologic phase, the virus spread
to the glands, skin, and other body parts,
including the salivary glands, from where it is
transmitted