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VIRUSES

Joy N. Bautista, RN, MPH, DRDM, MAN

VIRUS
Small obligate intracellular parasites,
which by definition contain either a
RNA or DNA genome surrounded by a
protective, virus-coded protein coat.
Depend on specialized host cells
supplying the complex metabolic and
biosynthetic machinery of eukaryotic or
prokaryotic cells for propagation

VIRAL STRUCTURE
Virion - a complete virus particle
Function - deliver viral DNA or RNA genome
into the host cell so that the genome can be
expressed (transcribed and translated) by the
host cell.
Viral genome - packaged inside a symmetric
protein capsid.
Nucleocapsid nucleoprotein + genome
Enveloped viruses - nucleocapsid is
surrounded by a lipid bilayer derived from the
modified host cell membrane and studded with
an outer layer of virus envelope glycoproteins.

METHODS OF
CLASSIFICATION
Configuration of the nucleic acid (ss or
ds, linear or circular).
Whether the genome consists of one
molecule of nucleic acid or is
segmented.
Whether the strand of ss RNA is sense
or antisense.
Site of viral capsid assembly.
Site of nucleocapsid envelopment in
enveloped viruses.

DNA VIRUSES

RNA VIRUSES

VIRAL EPIDEMIOLOGY
Entry into host cells to multiply
Transmission
Horizontal - between different
individuals through body surfaces,
blood stream, and arthropod bite
Vertical - between mother and
offspring either before, during, or
immediately after birth

DNA Viruses

Adenoviridae

Infections
Adults acute follicular conjunctivitis, epidemic
keratoconjunctivitis, cystitis and gastroenteritis
Infants acute febrile pharyngitis and
pharyngeal-conjunctival fever
Pathology droplet transmission with localized viral
multiplication in portals of entry
Oncogenecity r/t ability of virus to turn off
expression of genes in major histocompatibility
complex allowing them to grow into solid tumors
(adenoma)

Hepadnaviridae

Infections - Hepatitis B infection


Prodromal phase 2 weeks; fatigue, malaise, nv,
cough, h/a, low-grade fever, upper abdominal pain
Icteric phase jaundice, 2-6 weeks post-exposure
Recovery phase 6-8 weeks after exposure
Pathology transmission by exchange of body fluids
Cellular immune responses to infected hepatocytes
lead to continuous viral replication with cirrhosis
and hepatocellular CA
Oncogenecity nonspecific stimulation of active
regeneration and cirrhosis with genetic translocation
and chromosomal rearrangement

Herpesviridae
Alpha Herpesviridae Infections
Short reproductive cycle; very fast destruction of host cell
Produce latent infections in sensory nerve ganglia
HSV1 transmitted by kissing/contact with saliva
gingivostomatitis
HSV2 sexual transmission genital herpes, HS keratitis,
herpetic whitlows, herpes gladiotorum, neonatal HSV
infections
VZV droplet transmission
Chicken pox, herpes zoster, shingles,
Secondary bacterial infections, pneumonitis, hepatitis,
cutaneous infections, visceral complications

Herpesviridae
Beta Herpesviridae Infections
Limited number of host cells; very long reproductive life cycle;
infection takes a very long time to develop
Form latent infections in secretory glands, reticuloendothelial
cells, kidneys
CMV transmission via saliva, urine, breast milk, cervical
secretions
Congenital CMV syndrome hepatosplenomegaly,
retinitis, petechiae, purpura, hearing loss
Mononucleosis syndrome fever, malaise, atypical
lymphocytosis, pharyngitis, rarely cervical adenopathy and
hepatitis
Persistent infections salivary glands, breasts, kidneys,
endocervix, seminal vesicles, peripheral WBC

Herpesviridae
Gamma Herpesviridae Infections
Very limited number of host cells; replicate in
lymphoblastoid cells
EBV classic mononucleosis by intimate contact and
exchange of saliva
HHV-6 and HHV-7 exanthem subitum (roseola), kidney
transplant rejection, fulminant hepatitis, CNS infections
KS Kaposis sarcoma, AIDS-related lymphomas

Papovaviridae

Infections papilloma virus infections


Benign common warts, plantar warts, flat warts,
cervical flat warts, oral papillomas
Laryngeal papilloma
Condylomata acuminata anogenital warts in lower
female genital tract
Epidermodysplasia verruciformis
Pathology contact transmission with formation of
benign papillomas leading to epidermal thickening,
hyperplasia of s. spinosum, and hyperkeratosis
Oncogenecity cervical CA, penile and vulvar CA, CA of
the larynx, oropharynx, and tongue

Parvoviridae
Infections B19 virus infections
Erythema infectiosum
Prodrome 7-8 days; flu-like symptoms, h/a,
malaise, chills, fever
Latent no symptoms for 1 week
Clinical 17-18 days after; mild fever,
maculopapular rash (marked erythema of the
cheeks lsting about 1-3 weeks)
Aplastic crisis in patients with hemolytic diseases
Fetal loss and hydrops fetalis severe fetal anemia and
edema in fetus up to 12 weeks after maternal infection

Parvoviridae
Pathology transmission via respiratory route and blood
Viral replication in erythroid precursor cells with cell lysis
and loss of RBC from bone marrow
Immune response to virus produce erythema and arthralgia
Transplacental transmission damages fetal erythroid
precursor cells and cardiac myocytes

Poxviridae
Infections
Human monkey pox and molluscum - multiple firm, pearly, fleshcolored nodules, relatively painless and cause very little
constitutional disturbance.
Human cowpox and parapox - lesion develops at the site of
inoculation (usually the hand), and infection may be spread to other
sites such as the face and/or genitals by scratching.
Early lesions
Vesicular (cowpox) - very painful, particularly in young
children, usually causes pyrexia and marked
lymphadenopathy; this requires hospitalization.
Nodular (parapox) - painless and cause little
constitutional disturbance.
Lesions then become hemorrhagic crusting ulcers.

Poxviridae
Pathology
Transmission by direct contact through broken skin with dermal
hyperplasia and WBC infiltration
Cowpox and parapox - limited lymphatic spread; causes
lymphadenopathy and elicits an immune response.
Molluscum - circumscribed by a connective tissue capsule
Human monkey pox - acquired via the respiratory tract, and during
a 12-day incubation period viremia distributes infection to internal
organs, which are damaged by virus infection.
Spread to the skin initiates the clinical phase, and the
lesions progress through the classic stages of macule to
papule to vesicle to pustule to crust.
Lymphadenopathy of the cervical and inguinal areas.

RNA Viruses

Alphaviridae
Infections severe destructive CNS infections
(encephalitis) and painful arthritis syndromes
Venezuelan equine encephalitis
Eastern equine encephalitis
Western equine encephalitis
Semliki Forest viruses
Chikungunya
Onyongnyong, Mayaro, and Ross river virus
Sindbis viruses

Alphaviridae
Pathology mosquito-borne transmission leading to
viremia, fever, chills, malaise, arthritis
Maculopapular rash in 3-5 days
Migratory arthralgia in small joints
In severe infections neurologic involvement
Lethargy, somnolence, mild confusion, nuchal rigidity
Seizures, ataxia, paralysis, coma

Arenaviridae
Infections persistent silent infections in rodents and
severe, lethal, disseminated infections in humans
Severe hemorrhagic fever Lassa (W Africa), Junin (Argentina),
Machupo (Bolivia), Guanarito (Venezuela)
Lymphocytic choriomeningitis

Pathology transmission by contact with rodent urine

Bunyaviridae
Infections
Human fever, hemorrhagic fever, renal failure, encephalitis,
meningitis, blindness
La Crosse encephalitis fever, convulsions,
drowsiness, focal neurologic signs
Crimean-Congo hemorrhagic fever h/a, limb pain,
bleeding in multiple orifices
Hantavirus pulmonary syndrome fever, ARDS
Rift Valley fever fever, encephalitis, hemorrhagic
illness with retinal vasculitis
Domestic animals congenital defects
Pathology transmission by bite of arthropods

Caliciviridae
Infections
Human epidemics of diarrhea and vomiting
Abdominal cramps, myalgias, malaise, h/a, nausea,
low-grade fever
Animals mucocutaneous and respiratory tract lesions
Pathology
Ingestion of viral particles from contaminated water or food
Formation of transient mucosal lesion in proximal small
intestines

Coronaviridae
Infections common cold, mild URTI
Grow only in differentiated respiratory epithelium
Pathology droplet transmission
Vacuolation of infected cells
Damage to cilia with formation of syncytia
Stimulation of inflammation inflammatory mediators leads
to nasal secretion and swelling

Filoviridae
Infections hemorrhagic fever outbreaks from monkeys
Biological Level 4 agent very lethal
High mortality rates, person-to-person aerosol transmission,
no vaccines nor treatment
Agents Marburg, Ebola
Sudden onset fever, chills, h/a, myalgia, anorexia
Abdominal pain, sore throat, n/v, cough, arthralgia, diarrhea,
pharyngeal and conjunctival vasodilation
Dehydration, apathy, disorientation
Non-pruritic, maculopapular centripetal rash with erythema
and desquamation
Hemorrhage leading to hypovolemic shock and death

Filoviridae
Pathology airborne transmission
Necrosis of liver, spleen and lymph nodes
Extensive viral replication in tissue macrophages, interstitial
fibroblasts, and circulating monocytes/ macrophages

Flaviviridae
Infections from benign febrile infections to severe
hemorrhagic infections
Encephalitis
Yellow fever
Agents
Tick-borne tick-borne encephalitis
Mosquito-borne
Dengue
Encephalitis St. Louis, Japanese, Kunjin, Murray
Valley, West Nile
Yellow fever virus

Flaviviridae
Encephalitis Syndrome
SLE, JE, KV, MVE, WNV
Inoculation of virus in skin via saliva of infected arthropod
Viral replication in regional lymph nodes
Viremia leads to replication in neural and glial tissues
Neuronal degeneration and lymphocytic infiltration

Flaviviridae
Fever-Arthralgia-Rash Syndrome (Dengue)
Viral replication in macrophages at site of mosquito (Aedes
eagypti) bite
Replication in regional lymph nodes and reticuloendothelial
system

Dengue fever self-limiting, rarely with complications


Fever, h/a, vomiting, severe myalgia (3-9 days)
Maculopapular or morbiliform rash on trunk then to limbs and
face (3-5d after fever)
Fever, lymphadenopathy, granulocytopenia, thrombocytopenia
Petechiae, epistaxis, menorrhagia, + tourniquet test

Flaviviridae
Fever-Arthralgia-Rash Syndrome (Dengue)

Dengue henorrhagic fever d/t diffuse capillary leak with


hemoconcentration, thrombocytopenia, and DIC
Initial fever, rash, anorexia (3-5 days)
Shock phase hepatomegaly, hypotension, hemorrhagic
diathesis, complement activation, thrombocytopenia

Dengue shock syndrome decreased plasma volume d/t


increased vascular permeability
Causes clinical shock
Metabolic acidosis, hyperkalemia, death

Flaviviridae
Yellow Hemorrhagic Fever

Viral replication in reticuloendothelial cells esp in liver


parenchyma, adrenal glands, heart, kidneys
Liver damage midzonal necrosis and intracellular
eosinophilic deposits (Councilman bodies)
Pre-renal azotemia, ATN oliguria and AB imbalance
Myocardial fiber degeneration and myocarditis
Coagulation defects and DIC yellow fever
Death d/t severe toxicity, extensive mucosal and GI
hemorrhage, azotemia, shock

Orthomyxoviridae
Infections influenza; major complication = fatal pneumonia

Gene reassortment occurs if host cell gets infected with 2


different strains influenza pandemics vs. seasonal
influenza
Seasonal influenza d/t antigenic drifting (repeated minor
antigenic changes produce strains that retain a degree of
serologic relationship with original strain)
Influenza pandemic d/t antigenic shifting (major change
in surface antigens showing no serologic relationship to the
original strain)

Orthomyxoviridae
Pathology droplet transmission

Viral particles produce mucus liquefaction to aid in spread


Mucosal cell infection cell destruction and
desquamation
Edema and mononuclear cell infiltration
S/Sx fever, tracheitis, marked myalgia
h/a, chills, fever, malaise, anorexia, sore throat
Nonproductive cough, sneezing, rhinorhea, pharyngitis,
nasal obstruction, hoarseness, n/v/d, abdominal pain,
photophobia

Paramyxoviridae
Paramyxovirus

30-40% of all acute respiratory infections in young children


Causes parainfluenza, croup, bronchiolitis, pneumonia
Pathology
Direct person-to-person, droplet, and airborne
transmission
Localized infection in resp tract with extension into
paranasal sinuses, middle ear and LRT

Paramyxoviridae
Pneumoviruses

RSV respiratory syncytial virus


Infections
Infants bronchiolitis, pneumonia
Young children croup, tracheobronchitis
Others conjunctivitis, otitis media, exanthems on
trunk and face
Pathology
Direct person-to-person, droplet, and airborne
transmission

Paramyxoviridae
Morbiliviruses Mumps and Measles

Mumps infectious parotitis; nonpurulent inflammation of


salivary glands
Viral replication in epithelial cells with relocation in
salivary glands, testes, ovaries, pancreas, brain
S/Sx edematous, painful, enlarged parotid glands
Complications pancreatitis, meningitis, encephalitis,
hearing loss, orchitis, oophoritis

Paramyxoviridae
Morbiliviruses Mumps and Measles

Measles coryza, conjunctivitis, fever, rash


Viral replication in resp. tract and regional lymph nodes
with spread through RES
Prodromal phase IP 9-12 days; URTI, malaise, fever,
coryza, cough, conjunctivitis
Eruptive phase Koplik spots, maculopapular rash on
head then body and limbs (initially erythematous and
maculopapular before turning confluent)
Complications otitis media, pneumonia, croup,
bronchiolitis, giant cell pneumonia, postinfectious
measles encephalitis

Picornaviridae
Enteroviruses - oronasal transmission
Undifferentiated febrile illness, U/LRTI, GI infections,
conjunctivitis, skin and mucus membrane lesions
Infections of the CNS, muscles, heart, liver
EV-68 and 69 respiratory infections in young children
EV-70 epidemic and pandemic acute hemorrhagic
conjunctivitis
EV-71 meningitis, encephalitis, HFMD
May be transferred by fingers and inanimate objects

Picornaviridae
Rhinoviruses transmission via nasal secretions
Produce mild common colds with rhinorrhea, nasal
obstruction, fever, sore throat, cough, hoarseness
Pathology inflammatory changes with hyperemia, edema,
and columnar epithelial inflammation

Picornaviridae
Hepatitis A virus fecal-oral transmission
Viral hepatitis or infectious/epidemic hepatitis
Pathology limited to the liver
Conspicuous focal activation of sinusoidal lining cells .
Accumulations of lymphocytes and more histiocytes in
the parenchyma, often replacing hepatocytes lost by
cytolytic necrosis predominantly in the periportal areas .
Occasional coagulative necrosis in the form of
acidophilic bodies.
Focal degeneration.

Picornaviridae
Poliovirus airborne droplet transmission; present in throat
Viral tropism for epithelial cells of the GI and CNS
Produces aseptic meningitis
Viral replication
Alimentary phase oropharynx, intestinal mucosa
Lymphatic phase tonsils, Peyers patches (ileum),
deep cervical and mesenteric lymph nodes
Viremic phase bloodstream and regional lymph
nodes
Neurologic phase (rarely) spinal cord, brainstem
irreversible flaccid muscle paralysis

Picornaviridae
Coxsackievirus involves the motor neurons of brainstem and
spinal cord
Grp A outbreaks of HFMD
Rashes, vesicular lesions, herpangina
Acute lymphonodular pharyngitis, exanthema
Grp B
Pleurodynia fever, h/a, stabbing pain in chest or upper
abdomen
Viral pericarditis and myocarditis fever, tachycardia,
dyspnea, precordial pain
Neonatal myocarditis with CNS and liver involvement
lethargy, feeding problems, fever, cardiopulmonary distress

Picornaviridae
Echoviruses
Respiratory illnesses
Febrile illnesses with or without rash
Boston exanthema
Aseptic meningitis
Paralytic diseases
Occasional conjunctivitis

Reoviridae
Agents Rotavirus, Coltivirus, Orbivirus
Infections
Rotavirus - viral gastroenteritis
Other diarrheal diseases in young children such as
necrotizing enterocolitis, hemorrhagic gastroenteritis
Pathology fecal-oral transmission, ocassional waterborne or airborne routes
Coltivirus and Orbivirus Colorado tick fever
Diphasic fever, Kemero encephalitis, Orungo viremia,
Changuinola fever
Pathology arthropod bite transmission with
replication in regional lymph nodes

Retroviridae

Agents HTLV, HIV

Infections
Adult T-cell leukemia starts as asymptomatic
infections, lymphoproliferative disorders with
moderate lymphocytosis and aberrant lymphocytes
AIDS marked depletion of CD4 cells with
concomitant increase in suppressor T-cells
Tropic spastic paraparesis

Characteristic presence of reverse transcriptase to


transcribe RNA into DNA

Rhabdoviridae
Agents Rabies virus
Lyssavirus Lagos bat, Mokola, Duvenhage viruses
Vesiculovirus
Rabies
Incubation 5 days-2 years (average = 1-3 months)
Prodrome 2-10 days; malaise, fever, fatigue
Sore throat, cough, dyspnea
Anorexia, dysphagia, n/v/d, abdominal pain
h/a, vertigo, anxiety, apprehension, irritability,
nervousness, agitation, psychiatric disturbances
Photophobia, priapism, increased libido, insomnia,
nightmares, depression, encephalitis

Rhabdoviridae
Rabies
Acute neurologic period objective CNS dysfunction
Furious rabies hyperactivity (hydrophobia)
Dumb rabies paralysis
Fever, paresthesia, nuchal rigidity, muscle
fasciculations, focal and generalized convulsions,
hyperventilation, hypersalivation
Coma rapid irregular breathing, paralysis, respiratory
arrest
Death

Rhabdoviridae
Rabies Pathology
Transmission via bite of infected mammal
Viral entry and replication in PNS and muscle tissues
Viral translocation to the CNS with replication
Pass centrifugally to many tissues and organs, such as
the salivary glands
Mild congestion of the meninges

Togaviridae
Agents Rubella virus (German measles)
Infections
Rubella mild disease characterized by rash
Postnatal rubella mild, self-limited infection
Maculopapular rash on face and neck progressing
towards the legs and feet (3-5 days)
Low-grade feverlasting <24 hours
Postauricular, occipital, post. cervical
lymphadenopathy
Congenital rubella acquired during pregnancy
Stillbirth, spontaneous abortion
Congenital anomalies

Togaviridae
Pathology
Postnatal
Human reservoir with postnatal person-to-person
transmission via direct or droplet contact
Viral replication in respiratory tract with extension
into lymph nodes before spread to and replication in
target organs
Congenital
Rubella infection in 1st trimester
Transplacental invasion with fetal infection
Chromosomal abnormalities, slow cellular growth
rates, cell lysis and death in some cell types

UNCONVENTIONAL
VIRUSES
(PRIONS)

Prions

Smaller than conventional viruses mainly composed


of proteins (not DNA or RNA)
May produce the following diseases:
Unconventional encephalopathies
Kuru
Creutzfeldt-Jakob disease
Gerstmann-Straussler-Schenker syndrome
Fatal familial insomnia
Diseases in animals
Scrapie, transmissible mink encephalopathy
Chronic wasting disease, spongiform
encephalopathy

Prion Infections: Acute


Spongiform Encephalopathies

Characterized as slow infections


Prolonged incubation period (several months to
several years)
Progressive clinical course of disease always
leading to death
Pathologic lesions limited to a single organ
system
Limited natural host range

Prion Infections
Kuru
Cerebellar ataxia and shivering-like tremor leading to
complete motor incapacity with dysarthria and total loss of
speech and death within 1 year from onset
Ambulatory kuru subjective unsteadiness of gait and
stance
Postural instability, truncal tremor, titubation
Dysarthria, speech deterioration
Ataxic eye movements with convergent strabismus

Prion Infections
Kuru
Sedentary kuru inability to walk w/o complete support
More severe tremors and ataxia
Rigid limbs, clonus, coarse athetoid and choreiform
movements, exaggerated startle response
Emotional lability, mental slowing
Terminal kuru inability to sit up w/o complete support
Severe ataxia, tremors, dysarthria
EPS manifestations, urinary-fecal incontinence
Deep decubitus ulcers, hypostatic pneumonia
Death d/t inanition

Prion Infections
Scrapie
Natural scrapie in sheep and goats is characterized by the
presence of vacuolated neurons and extensive astrogliosis.
Apprehension, restlessness, hyperexcitability, and
aggressiveness, and some animals even manifest
apparent dementia.
Early - fine tremors of the head and neck.
Progressive - tremors become more generalized, involving
the whole body and producing shivering effect as
disturbances in locomotion.
Advanced stupor, visual impairment, excessive
salivation, urinary and fecal incontinence, and wasting
lassitude.

Prion Infections
Creutzfeldt-Jakob disease
Affects the cortical gray matter of the brain (>45yo)
Nervousness, behavioral changes, visual problems
Fatigue, weight loss
Anxiety, sleeplessness, malaise, headache
Vague psychic disturbances.
Frank dementia, memory loss, intellectual function, and
impaired judgment
Intermittent myoclonus
Cerebellar, extrapyramidal, or pyramidal symptoms
followed by mutism, rigidity, and death.

Prion Infections
Gerstmann-Straussler-Schenker syndrome
Similar to kuru; more amyloid-containing plaques than in
Creutzfeldt-Jakob disease
Degeneration of white matter with loss of neurons, glial
cells, and spongiform degeneration
May be iatrogenically transmitted via
Neurosurgery, corneal graft
Electrocorticography with a probe electrode
previously used and sterilized with alcohol and
formaldehyde
Human hormones prepared from pooled pituitary
glands of cadavers with minimum incubation
periods of <19 years and human dural grafts.

Prion Infections
Fatal Familial Insomnia
Inherited syndrome with an autosomal dominant pattern
of occurrence characterized by progressive severe
insomnia and dysautonomia with selective atrophy of two
thalamic nuclei.
Ataxia, myoclonus, and other signs resembling those of
CJD/GSS, and a few affected patients had spongiform
changes in the cerebral cortex.

Prion Infections Pathology

Affected cells dendritic and axonal processes, cell


bodies of neurons, astrocytes, oligodendrocytes
Mechanism progressive vacuolation
Astroglial hypertrophy and proliferation
Spongiform change of gray matter
Extensive neuronal dropout and loss
Ultrastructural alterations in plasma membrane
lining the vacuoles
Piled up neurofilaments in swollen nerve cels
Strange arrays of tubules in postsynaptic
processes

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