Poxviridae FINAL

8/6/2019 Poxviridae FINAL

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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 - +

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Poxviridae FINAL