Viral Infections of the Lung
Centers for Disease Control
Many pulmonary infections in man are caused by viruses such as influenza virus, adenovirus,
coronavirus, and herpesvirus. Viral infections of the lower respiratory tract occur in both normal and
immunocompromised hosts (not mutually exclusive). Table 1 provides a list of the most common
viral pathogens observed in these patient populations. Lung may also be involved as part of systemic
viral infection as seen for example with poxviridae, parvoviridae, and viral hemorrhagic fevers.
Table 1: Common Viral Infections in Immunocompetent and Immunocompromised Patients
The diagnosis of viral pneumonia, suspected by history and clinical manifestations, also can be
supported histopathologically, and the overall pattern of histopathologic lesions may suggest a specific
diagnosis. Many viruses can be identified in lung by examining the tissue response and cytopathic
changes. Some of these viruses cause recognizable tissue reaction patterns including necrotizing
tracheobrochitis, bronchiolitis, and interstitial pneumonia. A summary of the key diagnostic features
for the most common viral pathogens that cause a majority of pulmonary infections is provided in Table
Table 2: Diagnostic Features of Viral Pneumonias
| Family ||Virus|| Inclu- sions ||Description|| Tissue Reaction || Diagnostic Ultrastructural Features|
|Adenoviridae ||Adenovirus ||Yes ||Nuclear ||Necrotizing bronchiolitis; smudge cells; DAD ||70-90 nm nucleocapsids (NC) with a dense core are found in cell nuclei, sometimes in paracrystalline arrays.|
|Bunyaviridae ||Hantavirus ||No || ||Severe edema, early DAD ||Virions difficult to detect; characteristic NC granulofilamentous inclusions in endothelial cells|
|Coronaviridae ||SARS ||No || ||Interstitial pneumonia;occasional multinucleation ||Spherical, enveloped virions, approx. 75, but up to 160 nm in diameter, accumulate in cytoplasmic vesicles, and are often found adherent to the plasma membrane.|
|Herpesviridae ||Cyto- megalovirus ||Yes ||Nuclear and cytoplasmic ||Interstitial pneumonia; DAD; cytomegaly ||100 nm viral NCS are found in cell nuclei; in cytoplasm, tegument surrounds the nucleocapsids and enveloped virions, 120-200 nm, are found in Golgi cisternae and extracellularly|
| ||Herpes Simplex ||Yes ||Nuclear ||DAD; necrosis and rare multinucleation |
| ||Varicella- zoster ||Yes ||Nuclear ||DAD; necrosis, and rare multinucleation |
|Ortho- myxoviridae ||Influenza ||No || ||DAD; necrotizing bronchiolitis ||Filamentous virions, 80-100 nm in diameter, are composed of enveloped, filamentous NCs found budding at the plasma membrane of infectious cells. Cytoplasmic and nuclear NCs are sometime seen.|
|Para- myxoviridae ||Measles||Yes ||Nuclear and cytoplasmic ||Interstitial pneumonia with multinucleation DAD ||Paramyxovirinae (measles, nipah, PI) are enveloped, pleomorphic virions, roughly 125-250 nm in diameter, consist of an enveloped aggregation of filamentous NC. The 18 nm wide NCs aligns under plasma membranes as virions bud into extracellular space. Pneumovirinae (RSV, HMPV) are somewhat smaller than Paramyxovirinae, the roughly spherical enveloped particles average 90-130 nm, and contain 14 nm wide NCs.|
| ||Nipah ||Yes ||Nuclear and cytoplasmic ||Interstitial pneumonia with multinucleation and DAD|
| ||Para- influenza (PI) ||Yes ||Cytoplasmic ||DAD; interstitial pneumonia with occasional multinucleation |
| ||Respir- atory syncytial virus (RSV) ||Yes ||Cytoplasmic ||Necrotizing bronchiolitis, interstitial pneumonia with occasional multinucleation |
| ||Human Meta- pneumonia (HMPV)|| || ||Recently described; human pathology not yet described |
Only certain viruses can cause cytopathic changes that are morphologically distinctive
enough to enable the pathologist to recognize a specific diagnosis on routine histologic examination
of lung specimens. With the availability of special diagnostic techniques, such as
immunohistochemistry (IHC) and in situ hybridization (ISH), many viruses can be detected in
formalin-fixed, paraffin-embedded tissue samples even if specific viral inclusions cannot be found in
histologic examination of tissue sections. Among the techniques, IHC utilizing specific
antibodies can be routinely performed on formalin-fixed tissue and can enhance the pathologist's accuracy
in identifying organisms in tissue specimens. Some commercial sources for available antibodies to detect
the most prominent viral pathogens are provided in Table 3.
Table 3: Sources for Commercial Immunohistochemical Reagents
| Virus ||Commercial Sources|
|Herpes Simplex ||DAKO, Chemicon|
|Parvovirus ||Novocastra, Chemicon, DAKO|
|Respiratory syncytial virus ||Chemicon|
In addition to histologic pattern recognition, IHC, and ISH in tissue, several other diagnostic tests
are available to aid the pathologist. Cell culture techniques, serology, polymerase chain reaction
(PCR), and electron microscopy (EM) all play vital roles in the diagnosis of these infections.
While histologic techniques can be an excellent means of demonstrating organisms and more
sophisticated methods are available using fixed tissue, cultures remain essential for definitive
identification of the organism. Samples of all lung tissues should be routinely cultured for organisms
when viral pneumonia is suspected. The major advantage of using cell cultures in virologic diagnosis is
that it is a non-biased method for screening purposes that doesn't rely on availability of specific
antibodies or probes.
Likewise, electron microscopy (EM) offers the same utility as a broad scope diagnostic tool
and has been especially critical in outbreaks of unknown etiology. Recently, EM played a critical role
during the Nipah virus outbreak in 1999 and more recently, in the early recognition of a novel
coronavirus associated with the sudden acute respiratory syndrome (SARS) in 2003. The advantage of this
method is that viral particles may be demonstrated directly in clinical material or after amplification
in cell culture by negative stain and/or thin section electron microscopy. Like culture, EM is not
limited by narrow specificity of reagents or prior clinical bias.
During the course of the talk, an overview of the common pathologic findings present in viral
pneumonias will be presented along with discussion of current diagnostic testing modalities. Recent
experiences with sudden acute respiratory syndrome (SARS) and influenza associated deaths in the United
States among children will be discussed. General and specific references on viral infections are
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Viral Hemorrhagic Fevers
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