Viral Diseases of the Respiratory System

Colds

The common cold is caused by several different viruses and is the most common human viral infection.

Learning Objectives

Recognize the major viruses known to cause the common cold: rhinovirus, human parainfluenza virus and the human respiratory syncytial virus (RSV)

Key Takeaways

Key Points

  • Over 200 virus types have been found that cause the common cold, with rhinoviruses being the most common.
  • Rhinoviruses are a sub-type of picornavirus, a non-enveloped RNA virus, which is very small in size.
  • The symptoms of the common cold are not due to the viral infection directly but rather the bodies response to the virus.
  • There is no cure for the common cold, and in fact antibiotics which often prescribed are detrimental to patients.

Key Terms

  • serotypes: A group of microorganisms characterized by a specific set of antigens; serovar.
  • capsid: The outer protein shell of a virus.

The common cold (also known as nasopharyngitis, rhinopharyngitis, acute coryza, or a cold) is a viral infectious disease of the upper respiratory tract which affects primarily the nose. Symptoms include coughing, sore throat, runny nose, and fever which usually resolve in seven to ten days, with some symptoms lasting up to three weeks. Well over 200 viruses are implicated in the cause of the common cold. The most commonly implicated virus is a rhinovirus (30–80%), a type of picornavirus with 99 known serotypes. A picornavirus is a virus belonging to the family Picornaviridae. Picornaviruses are non-enveloped RNA viruses with an icosahedral capsid. The name is derived from pico, meaning small, and RNA, referring to the ribonucleic acid genome, so “picornavirus” literally means small RNA virus. Others include: coronavirus (10–15%), human parainfluenza viruses, human respiratory syncytial virus, adenoviruses, enteroviruses, and metapneumovirus. Frequently more than one virus is present.

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Coronaviruses: Coronaviruses are a group of viruses that have a halo, or crown-like (corona) appearance when viewed under an electron microscope. If you have a cold 10-15% of the time it is caused by a virus like this.

The symptoms of the common cold are believed to be primarily related to the immune response to the virus. The mechanism of this immune response is virus specific. For example, the rhinovirus is typically acquired by direct contact; it binds to human ICAM-1 receptors through unknown mechanisms to trigger the release of inflammatory mediators. These inflammatory mediators then produce the symptoms. It does not generally cause damage to the nasal epithelium. The respiratory syncytial virus (RSV) on the other hand is contracted by both direct contact and air born droplets. It then replicates in the nose and throat before frequently spreading to the lower respiratory tract. RSV does cause epithelium damage. Human parainfluenza virus typically results in inflammation of the nose, throat, and bronchi. In young children when it affects the trachea it may produce the symptoms of croup due to the small size of their airway.

No cure for the common cold exists, but the symptoms can be treated. Antibiotics have no effect against viral infections and thus have no effect against the viruses that cause the common cold. Due to their side effects they cause overall harm; however, they are still frequently prescribed.It is the most frequent infectious disease in humans with the average adult contracting two to three colds a year and the average child contracting between six and twelve. These infections have been with humanity since antiquity.

Viral Pneumonia

Viral pneumonia, one of the two leading causes of pneumonia, more commonly affects children.

Learning Objectives

Outline the route of infection for a virus that causes pneumonia

Key Takeaways

Key Points

  • Viral pneumonia is caused by both viral infection which leads to cell death. The body’s response to clear the cellular debris leads to further inflammation and the blockage of respiration.
  • Many different viruses can cause viral pneumonia, but they all enter the lungs and damage the alveoli.
  • The best prevention for viral pneumonia is to vaccinate against the viruses that can cause pneumonia.

Key Terms

  • Alveoli: alveolus (plural alveoli) a small air sac in the lungs, where oxygen and carbon dioxide are exchanged with the blood.
  • cytokines: Regulatory proteins that function in the regulation of the cells involved in immune system function
  • apoptosis: The process of programmed cell death by which cells undergo an ordered sequence of events which lead to death of the cell. This occurs during growth and development of the organism, as a part of normal cell aging, or as a response to cellular injury.

Pneumonia is an inflammatory condition of the lung that particularly affects microscopic air sacs (alveoli). It is associated with fever and chest symptoms, and it appears as a lack of space on a chest x-ray. The inflammation may be caused by infection from viruses, bacteria, or other microorganisms. Less commonly, it is caused by certain drugs and other conditions. Viruses and bacteria are the two leading causes of pneumonia, while fungi and parasites are less common. Viruses are the most common cause of pneumonia in children, while bacteria are the most common cause in adults.

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Symptoms of pneumonia: Typical symptoms associated with pneumonia.

How Viruses Cause Pneumonia

Many types of viral infections can cause pneumonia, but in order to do this, these viruses must first invade cells in order to reproduce. Typically, a virus will reach the lungs by traveling in droplets through the mouth and nose during inhalation. Once there, the virus will invade the cells that line the airways and the alveoli. This invasion often leads to cell death, in which either the virus directly kills the cell, or the cell self-destructs through apoptosis. Further damage to the lungs occurs when the immune system responds to the infection. White blood cells, in particular lymphocytes, are responsible for activating a variety of chemicals (cytokines) which cause fluid to leak into the alveoli. The combination of cellular destruction and fluid-filled alveoli interrupts the transportation of oxygen into the bloodstream. Thus, in large part, as with other viral infections, it is the body’s response to the virus that causes the symptoms of pneumonia, and not necessarily the viral infection itself. In addition to their effects on the lungs, many viruses affect other organs and can lead to illnesses that affect other bodily functions. Viruses also make the body more susceptible to bacterial infection. For this reason, bacterial pneumonia often complicates viral pneumonia.

Which Viruses Cause Pneumonia

Common viruses that cause pneumonia include influenza viruses A and B, respiratory syncytial viruses (RSV), and human parainfluenza viruses (hPIV), the last of which particularly affects children. Rarer viruses that commonly cause pneumonia include adenoviruses (in military recruits), metapneumoviruses, and severe acute respiratory syndrome virus (SARS coronavirus). Viruses that primarily cause other diseases, but sometimes cause pneumonia, include herpes simplex virus (HSV, mainly in newborns), varicella- zoster virus (VZV), measles virus, rubella virus, and cytomegalovirus (CMV, mainly in people with immune system problems). In children with pneumonia, the most commonly identified agents are respiratory syncytial virus, rhinovirus, human metapneumovirus, human bocavirus, and parainfluenza viruses. Because of this, the best prevention against viral pneumonia is vaccination against influenza, adenovirus, chickenpox, herpes zoster, measles, and rubella.

Respiratory Syncytial Virus Infection

Human respiratory syncytial virus (RSV) causes respiratory tract infections in humans.

Learning Objectives

Recognize the traits associated with the human respiratory syncytial virus (RSV) and its mode of infection

Key Takeaways

Key Points

  • RSV is a single stranded virus, the genome of which encodes 11 proteins which play different roles in RSV infection.
  • RSV can induce syncytia (aggregates of host cells), providing further fertile ground for RSV to propagate.
  • There is no direct treatment of RSV except to mitigate the symptoms, giving the patient’s body time to fight off the infection.

Key Terms

  • cannula: A hose or tube that connects directly to an oxygen (O2) bottle/source from the user’s nose, commonly used by aircraft pilots or others needing a direct oxygen breathing apparatus.
  • prophylactic: A medicine that preserves or defends against disease; a preventive.
  • hypertonic: Having a greater osmotic pressure than another.

Respiratory Syncytial Virus Infection

Human respiratory syncytial virus (RSV) is a virus that causes respiratory tract infections. It is a major cause of lower respiratory tract infections and hospital visits during infancy and childhood. A prophylactic medication (not a vaccine) exists for preterm-birth (under 35 weeks gestation) infants, and for infants with a congenital heart defect or bronchopulmonary dysplasia. Of those infected with RSV, 2–3% will develop bronchiolitis, necessitating hospitalization.

RSV is a negative-sense, single-stranded RNA virus of the family Paramyxoviridae, which includes common respiratory viruses such as those causing measles and mumps. RSV is a member of the paramyxovirus subfamily Pneumovirinae. RSV has ten genes encoding 11 proteins. There are two open reading frames of M2. NS1 and NS2 inhibit type I interferon activity. N encodes the nucleocapsid protein that associates with the genomic RNA forming the nucleocapsid. M encodes the matrix protein required for viral assembly. SH, G and F form the viral coat. The G protein is a surface protein; it functions as the attachment protein, the protein which attaches the virus to target cells. The F protein is another important surface protein. RSV’s name comes from the fact that F proteins on the surface of the virus cause the cell membranes on nearby cells to merge, forming syncytia.

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Syncytium: The mass or “ball” of cells in the middle of the image are a syncytium of cells that formed due to infection by the HIV virus.

Syncytia are aggregates of cells that can form when cells are infected with certain types of viruses, notably HIV and paramyxoviruses such as RSV. During infection, viral fusion proteins used by the virus to enter the cell are transported to the cell surface where they can cause the host cell membrane to fuse with neighboring cells. This presumably works to the virus’s advantage, as aggregates of target cells provide more hosts for the virus to infect and multiply. F proteins also mediate viral fusion, allowing entry of the virus into the cell cytoplasm and also allowing the formation of syncytia. Antibodies directed at the F protein are neutralizing. M2 is the second matrix protein required for viral transcription; it encodes M2-1 (elongation factor) and M2-2 (transcription regulation), while L encodes the RNA polymerase. The phosphoprotein P is a cofactor for L. The genome is transcribed sequentially from NS1 to L with reduction in expression levels along its length.

Treatment of RSV is limited to supportive care, including oxygen therapy. Studies of nebulized hypertonic saline (HS) have shown that the “use of nebulized 3% HS is a safe, inexpensive, and effective treatment for infants hospitalized with moderately severe viral bronchiolitis” where “RSV accounts for the majority of viral bronchiolitis cases. ” Supportive care includes fluids and oxygen until the illness runs its course. Increased airflow, humidified and delivered via nasal cannula, may be supplied in order to reduce the effort required for respiration.

Coryza and Influenza

Influenza is an infectious disease caused by RNA viruses of the family Orthomyxoviridae that affects birds and mammals.

Learning Objectives

Differentiate between the respiratory system disorders of influenza and coryza

Key Takeaways

Key Points

  • The most common symptoms of the disease are chills, fever, sore throat, muscle pains, severe headache, coughing, weakness/fatigue, and general discomfort.
  • Influenza is transmitted through the air by coughs or sneezes, by direct contact with bird droppings or nasal secretions, or through contact with contaminated surfaces.
  • Coryza is a word describing the symptoms of a cold and refers to the inflammation of the mucous membranes lining the nasal cavity which usually gives rise to the symptoms of congestion.

Key Terms

  • coryza: Inflammation of the mucous membranes lining the nasal cavity, usually causing a running nose, nasal congestion, and loss of smell.
  • RNA virus: Any of many viruses that possess ribonucleic acid as their genetic material and do not replicate using DNA.
  • influenza: An acute contagious disease of the upper airways and lungs, caused by a virus, which rapidly spreads around the world in seasonal epidemics.

Influenza, commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae that affects birds and mammals. The most common symptoms of the disease are chills, fever, sore throat, muscle pains, severe headache, coughing, weakness/fatigue, and general discomfort. Although it is often confused with other influenza-like illnesses, especially the common cold, influenza is a more severe disease than the common cold. The general symptoms of influenza are summarized in.

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Symptoms of influenza: Symptoms of influenza with fever and cough the most common symptoms.

Typically, influenza is transmitted through the air by coughs or sneezes, creating aerosols containing the virus. Influenza can also be transmitted by direct contact with bird droppings or nasal secretions, or through contact with contaminated surfaces. Reasonably effective ways to reduce the transmission of influenza include good personal health and hygiene habits such as: not touching your eyes, nose or mouth; frequent hand washing, covering coughs and sneezes, avoiding close contact with sick people and staying home yourself if you are sick.

Vaccinations against influenza are usually made available to people in developed countries. The most common human vaccine is the trivalent influenza vaccine (TIV) that contains purified and inactivated antigens against three viral strains. Typically, this vaccine includes material from two influenza A virus subtypes and one influenza B virus strain. The TIV carries no risk of transmitting the disease, and it has very low reactivity. A vaccine formulated for one year may be ineffective in the following year, since the influenza virus evolves rapidly, and new strains quickly replace the older ones.

Influenza viruses A, B, and C are very similar in overall structure and a diagram of the structure of the virus can be seen in Figure 2. The viral particles of all influenza viruses are similar in composition. They are made of a viral envelope containing two main types of glycoproteins, wrapped around a central core. The central core contains the viral RNA genome and other viral proteins that package and protect this RNA. RNA tends to be single stranded, but in special cases it is double. Unusually for a virus, its genome is not a single piece of nucleic acid but seven or eight pieces of segmented negative-sense RNA. Each piece of RNA contain either one or two genes, which code for a gene product (protein). Hemagglutinin (HA) and neuraminidase (NA) are the two large glycoproteins on the outside of the viral particles. HA is a lectin that mediates binding of the virus to target cells and entry of the viral genome into the target cell, while NA is involved in the release of progeny virus from infected cells, by cleaving sugars that bind the mature viral particles. Furthermore, they are antigens to which antibodies can be raised. Influenza A viruses are classified into subtypes based on antibody responses to HA and NA. These different types of HA and NA form the basis of the H and N distinctions in, for example, H5N1. There are 16 H and 9 N subtypes known, but only H 1, 2, and 3, and N 1 and 2 are commonly found in humans.

Antiviral medication can be effective, but some strains of influenza can show resistance to the standard antiviral drugs. The two classes of antiviral drugs used against influenza are neuraminidase inhibitors and M2 protein inhibitors (adamantane derivatives). Neuraminidase inhibitors are currently preferred for flu virus infections since they are less toxic and more effective.

Coryza is a word describing the symptoms of a “cold. ” It describes the inflammation of the mucous membranes lining the nasal cavity which usually gives rise to the symptoms of nasal congestion and loss of smell, among other symptoms. Coryza may not always have an infectious or allergenic etiology and can be due to something as innocuous as a cold wind, spicy food, or tender points in the muscles of the neck such as the sternocleidomastoid. It is also a symptom of narcotic withdrawal. Coryza is classically used in association with the “four Cs” of measles infection: cough, conjunctivitis, Koplik’s spots, and coryza.

Treatment of coryza depends on etiology. Coryza from any allergic causes usually gets relieved if contact with the allergen (dust, pollen, cold wind, etc.) is avoided. Nasal sprays, antihistamines, and decongestants are beneficial. However, if it is due to any virus it usually takes three to seven days to improve.