How Cold Viruses Cause Disease

Viruses cause infection by overcoming the body's complex defense system. The body's first line of defense is mucus, produced by the membranes in the nose and throat. Mucus traps the material we inhale: pollen, dust, bacteria, viruses. When a virus penetrates the mucus and enters a cell, it commandeers the protein-making machinery to manufacture new viruses which, in turn, attack surrounding cells.

Cold symptoms: the body fights back. Cold symptoms are probably the result of the body's immune response to the viral invasion. Virus-infected cells in the nose send out signals that recruit specialized white blood cells to the site of the infection. In turn, these cells emit a range of immune system mediators such as kinins. These chemicals probably lead to the symptoms of the common cold by causing swelling and inflammation of the nasal membranes, leakage of proteins and fluid from capillaries and lymph vessels, and the increased production of mucus. Kinins and other mediators released by immune system cells in the nasal membranes are the subject of intensive research. Researchers are examining whether drugs to block these mediators, or the receptors on cells to which they bind, might benefit people with colds.

How Colds are Spread

Depending on the virus type, any or all of the following routes of transmission may be common:

· Touching infectious respiratory secretions on skin and on environmental surfaces and then touching the eyes or nose.

· Inhaling relatively large particles of respiratory secretions transported briefly in the air.

· Inhaling droplet nuclei: smaller infectious particles suspended in the air for long periods of time.

Research on rhinovirus transmission. Much of the research on the transmission of the common cold has been done with rhinoviruses, which are shed in the highest concentration in nasal secretions. Studies suggest a person is most likely to transmit rhinoviruses in the second to fourth day of infection, when the amount of virus in nasal secretions is highest. Researchers have also shown that using aspirin to treat colds increases the amount of virus shed in nasal secretions, possibly making the cold sufferer more of a hazard to others.

NIAID grantees have found that rhinoviruses from nasal secretions can be transferred easily from the hands of an infected person to those of another--by shaking hands, for instance--or to a surface such as a doorknob or telephone that is then touched by another person. By touching one's eyes or nose with the fingers, something most people do many times a day, the susceptible person can be "self-inoculated." Other studies suggest rhinovirus colds can be transmitted through the air.

Preventing Transmission

Handwashing is the simplest and most effective way to keep from getting rhinovirus colds. Not touching the nose or eyes is another. Individuals with colds should always sneeze or cough into a facial tissue, and promptly throw it away. If possible, one should avoid close, prolonged exposure to persons who have colds.

Because rhinoviruses can survive up to three hours outside the nasal passages on inanimate objects and skin, cleaning environmental surfaces with a virus-killing disinfectant might help prevent spread of infection.

A cold vaccine? The development of a vaccine that could prevent the common cold has reached an impasse because of the discovery of many different cold viruses. Each virus carries its own specific antigens, substances that induce the formation of specific protective proteins (antibodies) produced by the body. Until ways are found to combine many viral antigens in one vaccine, or take advantage of the antigenic cross-relationships that exist, prospects for a vaccine are dim. Evidence that changes occur in common-cold virus antigens further complicate development of a vaccine. Such changes occur in some influenza antigens and make it necessary to alter the influenza vaccine each year.

Treatment

Only symptomatic treatment is available for uncomplicated cases of the common cold: bed rest, plenty of fluids, gargling with warm salt water, petroleum jelly for a raw nose, and aspirin or acetaminophen to relieve headache or fever.

A word of caution:several studies have linked the use of aspirin to the development of Reye's syndrome in children recovering from influenza or chickenpox. Reye's syndrome is a rare but serious illness that usually occurs in children between the ages of three and 12 years. It can affect all organs of the body, but most often injures the brain and liver. While most children who survive an episode of Reye's syndrome do not suffer any lasting consequences, the illness can lead to permanent brain damage or death. The American Academy of Pediatrics recommends children and teenagers not be given aspirin or any medications containing aspirin when they have any viral illness, particularly chickenpox or influenza. Many doctors recommend these medications be used for colds in adults only when headache or fever is present. However, researchers also have found aspirin and acetaminophen can suppress certain immune responses and increase nasal stuffiness in adults.

Nonprescription cold remedies, including decongestants and cough suppressants may relieve some cold symptoms but will not prevent, cure or even shorten the duration of illness. Moreover, most have some side effects, such as drowsiness, dizziness, insomnia or upset stomach, and should be taken with care.

Antihistamines generally don't relieve cold symptoms, because the body makes inflammatory chemicals other than histamine when attacked by a cold virus.

Antibiotics do not kill viruses. These prescription drugs should be used only for rare bacterial complications, such as sinusitis or ear infections, that can develop as secondary infections. The use of antibiotics "just in case" will not prevent secondary bacterial infections.

Does vitamin C have a role? Many people are convinced that taking large quantities of vitamin C will prevent colds or relieve symptoms. To test this theory, several large-scale, controlled studies involving children and adults have been conducted. To date, no conclusive data has shown that large doses of vitamin C prevent colds. The vitamin may reduce the severity or duration of symptoms, but definitive evidence is lacking.

Taking vitamin C over long periods of time in large amounts may be harmful. Too much vitamin C can cause severe diarrhea, a particular danger for elderly people and small children. In addition, too much vitamin C distorts results of tests commonly used to measure the amount of glucose in urine and blood. Combining oral anticoagulant drugs and excessive amounts of vitamin C can produce abnormal results in blood-clotting tests.

Inhaling steam also has been proposed as a treatment of colds on the assumption that increasing the temperature inside the nose inhibits rhinovirus replication. Recent studies found that this approach had no effect on the symptoms or amount of viral shedding in individuals with rhinovirus colds. However, steam may temporarily relieve symptoms of congestion associated with colds.

Interferon-alpha has been studied extensively for the treatment of the common cold. Investigators have shown interferon, given in daily doses by nasal spray, can prevent infection and illness. However, interferon causes unacceptable side effects such as nosebleeds and does not appear useful in treating established colds. Most cold researchers are concentrating on other approaches to combatting cold viruses.

NIAID Research

In laboratories in Bethesda, Md., and at grantee institutions nationwide, NIAID supports basic research on the structure of viruses that cause colds and cold-like diseases, and on their disease-causing mechanisms. The institute provides rhinovirus research materials to investigators, and has made its nationwide network of Vaccine and Treatment Evaluation Units available for clinical studies of potential new treatments.

NIAID-supported researchers have pioneered the use of X-ray crystallography to look at the atomic structure of viruses. The ability to picture the rhinovirus at this level and study its three-dimensional structure has revolutionized the design and testing of new antiviral drugs.

The researchers have shown rhinoviruses all share a common structure--a rhinovirus canyon--required for attachment to susceptible cells. These canyons are not accessible to attack by antibodies. Investigators are using X-ray crystallography to develop new drugs that snugly fit into and change the shape of the rhinovirus canyon, making the virus non-infectious.

Also, scientists have identified the docking molecule on cells to which the rhinovirus canyon attaches. This molecule is known as the intracellular adhesion molecule-1 (ICAM-1). NIAID-supported studies suggest that ICAM-1, or ICAM-1 coupled to an antibody, might be used to disrupt rhinoviruses and prevent their replication.

NIAID-funded studies of kinins and other mediators released in the nasal membranes are underway to further illuminate the sequence of events that occur between infection with a cold virus and the onset of symptoms. Recently, for example, investigators found increased levels of interleukin-1 (IL-1) in the nasal secretions of people with experimentally induced rhinovirus colds. The researchers speculate that IL-1 could play a number of roles in the development of the common cold, including the recruitment of immune system cells to the nasal mucosa.

The Outlook

Thanks to basic research, scientists know more about the rhinovirus than almost any other virus, and have powerful new tools for developing antiviral drugs. Although the common cold may never be uncommon, further investigations offer the hope of reducing the huge burden of this universal problem.

Asperger Syndrome