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Poxviridae Introduction
Poxviruses are the largest and mostcomplex of viruses. The family
encompasses a large group of agents that
are similar morphologically and share a
common nucleoprotein antigen.
Infections with most poxviruses are
characterized by a rash, although lesions
induced by some members of the family
Even though smallpox was declarederadicated from the world (in 1980) after an
intensive campaign coordinated by the
World Health Organization, there is
concern that the virus could be reintroduced
as a biologic weapon.
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Structure & Composition Poxviruses are large enough to be seen as
featureless particles by light microscopy.
By electron microscopy, they appear to be
brick-shaped measuring about 400 x 230
nm. Their structure is complex andconforms to neither icosahedral nor helical
symmetry. The external surface of
particles contains ridges.
There is an outer lipoprotein membrane, or
envelope, that encloses a core and two
structures of unknown function called
lateral bodies
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Classification
Poxviruses are divided into two subfamilies based on whether
they infect vertebrate or insect hosts.
The vertebrate poxviruses fall into eight genera, with the
members of a given genus displaying similar morphology and
host range as well as some antigenic relatedness.
Most of the poxviruses that can cause disease in humans are
contained in the genera Orthopoxvirus and Parapoxvirus;
there are also several that are classified in the genera
Yatapoxvirus and Molluscipoxvirus (Table 2)
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Table 2. Poxviruses Causing Disease in Humans.
Genus Virus Primary Host Disease
Orthopoxvirus Variola Humans Smallpox (now eliminated)
Vaccinia Humans Localized lesion; used for
smallpox vaccination
Buffalopox Water buffalo Human infections rare; localized
lesion
Monkeypox Rodents, monkeys Human infections rare;
generalized disease
Cowpox Cows Human infections rare; localizedulcerating lesion
Parapoxvirus Orf Sheep Human infections rare; localized
lesionPseudocowpox Cows
Bovine papular stomatitis Cows
Molluscipoxvirus Molluscum contagiosum Humans Many benign skin nodules
Yatapoxvirus Tanapox Monkeys Human infections rare; localized
lesion
Yabapox Monkeys Human infections very rare and
accidental; localized skin tumors
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Poxvirus ReplicationThe replication cycle of vaccinia virus is
summarized in Figure. Poxviruses are
unique among DNA viruses in that the
entire multiplication cycle takes place in
the cytoplasm of infected cells. It is
possible, however, that nuclear factors
may be involved in transcription andvirion assembly. Poxviruses are further
distinguished from all other animal
viruses by the fact that the uncoating step
requires a newly synthesized, virus-
encoded protein.The "uncoating" protein that acts on the cores is among the more than
50 polypeptides made early after infection. The second-stage
uncoating step liberates viral DNA from the cores; it requires both
RNA and protein synthesis. The synthesis of host cell macromoleculesis inhibited at this stage.
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Pathogenesis & Pathology of Smallpox
The portal of entry of variola virus was the mucous membranes of
the upper respiratory tract. After viral entry, the following are
believed to have taken place: (1) primary multiplication in the
lymphoid tissue draining the site of entry; (2) transient viremia and
infection of reticuloendothelial cells throughout the body; (3) a
secondary phase of multiplication in those cells, leading to (4) a
secondary, more intense viremia; and (5) the clinical disease. By the sixth to ninth days, lesions in the mouth tended to ulcerate
and discharge virus. Thus, early in the disease, infectious virus
originated in lesions in the mouth and upper respiratory tract. Later,
pustules broke down and discharged virus into the environment of
the smallpox patient.
Histopathologic examination of the skin showed proliferation of the
prickle-cell layer. Those proliferated cells contained many
cytoplasmic inclusions with mononuclear cells,
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Pathogenesis & Pathology of Smallpox
Clinical Findings
The incubation period of variola (smallpox) was 1014 days. The onset was usually sudden. One to 5 days of fever and malaise
preceded the appearance of the exanthems, which began as macules,
then papules, then vesicles, and finally pustules.
These formed crusts that fell off after about 2 weeks, leaving pinkscars that faded slowly. In each affected area, the lesions were
generally found in the same stage of development (in contrast to
chickenpox).
A "Smallpox Recognition Card" prepared by the World Health
Organization shows the typical rash. Lesions were most abundant on
the face and less so on the trunk. In severe cases, the rash was
hemorrhagic. The case-fatality rate varied from 5% to 40%. In mild
variola, called variola minor, or in vaccinated persons, the mortality
rate was under 1%.
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Immunity All viruses within the Orthopoxvirus genus are so closely related
antigenically that they cannot be easily differentiated serologically.
Infection with one induces an immune response that reacts with all
other members of the group.
An attack of smallpox gave complete protection against reinfection.
Vaccination with vaccinia induced immunity against variola virus for
at least 5 years and sometimes longer. Antibodies alone are notsufficient for recovery from primary poxvirus infection. In the human
host, neutralizing antibodies develop within a few days after onset of
smallpox but do not prevent progression of lesions, and patients may
die in the pustular stage with high antibody levels. Cell-mediated
immunity is probably more important than circulating antibody..
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Laboratory Diagnosis
Several tests are available to
confirm the diagnosis of
smallpox. Now that thedisease is presumably
eradicated, it is important to
diagnose any cases that
resemble smallpox. The tests
depend upon direct
microscopic examination of
material from skin lesions,
recovery of virus from the
patient, identification ofviral DNA or antigen from
the lesion, and, least
importantly, demonstration
of antibody in the blood.
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Picornaviruses Picornaviruses represent a very large virus family with respect to
the number of members but one of the smallest in terms of virion
size and genetic complexity.
They include two major groups of human pathogens:
enteroviruses and rhinoviruses. Enteroviruses are transient
inhabitants of the human alimentary tract and may be isolated
from the throat or lower intestine.
Rhinovirus Group
Rhinoviruses are the common cold viruses. They are the most
commonly recovered agents from people with mild upper
respiratory illnesses. They are usually isolated from nasalsecretions but may also be found in throat and oral secretions.
These virusesas well as coronaviruses, adenoviruses,
enteroviruses, parainfluenza viruses, and influenza viruses
cause upper respiratory tract infections, including the common
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Table 3. Important Properties of Picornaviruses.
Virion: Icosahedral, 2830 nm in diameter, contains 60 subunits
Composition: RNA (30%), protein (70%)
Genome: Single-stranded RNA, linear, positive-sense, 7.28.4 kb in size, MW 2.5
million, infectious, contains genome-linked protein (VPg)
Proteins: Four major polypeptides cleaved from a large precursor polyprotein.
Surface capsid proteins VP1 and VP3 are major antibody-binding sites. VP4 is aninternal protein.
Envelope: None
Replication: Cytoplasm
Outstanding characteristics: Family is made up of many enterovirus and rhinovirus
types that infect humans and lower animals, causing various illnesses ranging from
poliomyelitis to aseptic meningitis to the common cold.
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Rhinovirus
Classification
Human rhinovirus isolates are numbered sequentially.More than 100 species are known. Isolates within a
species share more than 70% sequence identity within
certain protein-coding regions.
Human rhinoviruses can be divided into major and minor
receptor groups. Viruses of the major group use
intercellular adhesion molecule-1 (ICAM-1) as receptor
and those of the minor group bind members of the low-
density lipoprotein receptor (LDLR) family.
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Pathogenesis The virus enters via the upper respiratory tract.
High titers of virus in nasal secretionswhich can be
found as early as 24 days after .
Thereafter, viral titers fall, although illness persists. In
some instances, virus may remain detectable for 3 weeks.
There is a direct correlation between the amount of virusin secretions and the severity of illness.
Replication is limited to the surface epithelium of the nasal
mucosa. Biopsies have shown that histopathologic changes
are limited to the submucosa and surface epithelium.These include edema and mild cellular infiltration. Nasal
secretion increases in quantity and in protein
concentration.
Rhinoviruses rarely cause lower respiratory tract disease.
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Immunity
Neutralizing antibody to the infecting virus develops in serum an
secretions of most persons(ranged from 37% to over 90%).
Antibody develops 721 days after infection; the time of
appearance of neutralizing antibody in nasal secretions parallels
that of serum antibodies. Because recovery from illness usually
precedes appearance of antibodies, it seems that recovery is not
dependent on antibody.
However, antibody may accomplish final clearance of infection.
Serum antibody persists for years but decreases in titer.
Treatment & Control
No specific prevention method or treatment is available.
Antiviral drugs are thought to be a more likely control measure for
rhinoviruses because of the problems with vaccine development.
A 5-day course of high doses of intranasal interferon-alfa has been
shown to be effective in preventing the spread of rhinoviruses .
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Orthomyxoviruses Introduction
Respiratory illnesses are responsible for more than half of all
acute illnesses each year in the United States.
TheOrthomyxoviridae (influenza viruses) are a major
determinant of morbidity and mortality caused by respiratory
disease, and outbreaks of infection sometimes occur in
worldwide epidemics.
Influenza has been responsible for millions of deaths
worldwide.
Influenza type A is antigenically highly variable and isresponsible for most cases of epidemic influenza. Influenza type
B may exhibit antigenic changes and sometimes causes
epidemics. Influenza type C is antigenically stable and causes
only mild illness in immunocompetent individuals
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Table3. Important Properties of Orthomyxoviruses.1
Virion: Spherical, pleomorphic, 80120 nm in diameter (helical nucleocapsid, 9 nm)
Composition: RNA (1%), protein (73%), lipid (20%), carbohydrate (6%)
Genome: Single-stranded RNA, segmented (eight molecules), negative-sense, 13.6 kb
overall size
Proteins: Nine structural proteins, one nonstructural
Envelope: Contains viral hemagglutinin (HA) and neuraminidase (NA) proteins
Replication: Nuclear transcription; capped 5' termini of cellular RNA scavenged as
primers; particles mature by budding from plasma membrane
Outstanding characteristics:
Genetic reassortment common among members of the same genus
Influenza viruses cause worldwide epidemics
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A comparison of influenza A virus with other viruses that infect the human respiratory tract is shown in Table 393. Influenza virus is
considered here.
Table -4. Comparison of Viruses that Infect the Human Respiratory Tract.Virus Disease Number of Serotypes Lifelong
Immunity
to Disease
Vaccine
Available
Viral Latency
RNAviruses
Influenza A virus Influenza Many No + -
Parainfluenza virus Croup Many No - -
Respiratory syncytial virus Bronchiolitis One No - -
Rubella virus Rubella One Yes + -
Measles virus Measles One Yes + -
Mumps virus
Parotitis, meningitis One Yes + -
Rhinovirus Common cold Many No - -
Coronavirus Common cold Many No - -
CoxsackievirusHerpangina, pleurodynia Many No - -
DNAviruses
Herpes simplex virus type 1 Gingivostomatitis One No - +
Epstein-Barr virusInfectious mononucleosis One Yes - +
Varicella-zoster virusChickenpox, shingles One
Yes1+ +
AdenovirusPharyngitis, pneumonia Many No - +