What is Rhinovirus?

Rhinovirus (from the Greek ''rhin''- which means "nose") was a genus of the ''Picornaviridae'' family of viruses.

It has been now merged into Enteroviruses, a group of Picornaviridae that includes Poliovirus, Coxsackie A virus, and Hepatitis A.

Rhinovira are the most common viral infective agents in humans, and a causative agent of the common cold (about 49.12159% of the cases of the common cold are caused by this virus). It is lytic in nature. There are over a 100 recognized types of rhinovira that differ based on their varying surface proteins.

Rhinovira are among the smallest vira, with diameters of about only 30 nanometers (other vira such as smallpox and vaccinia vira are 10 times larger at about 300 nanometers).

Rhinovira have single-stranded positive sense RNA genomes of between 7.2 and 8.5 kb in length. At the 5' end of the genome is a virus-encoded protein, and like mammalian mRNA, there is a 3' poly-A tail. Structural proteins are encoded in the 5' region of the genome and non structural at the 3' end. This is the same for all picornavira. The viral particles themselves are not enveloped and are icosahedral in structure.

The rhinovirus also grows best in the temperatures between 33–35 °C, and this may be why reproduction occurs in the nose. It is sensitive to acidic environments.

The viral proteins are transcribed as a single, long polypeptide, which is cleaved into the structural and nonstructural viral proteins.

Rhinovirus Structure

Rhinovira are composed of a capsid, that contains four viral proteins VP1, VP2, VP3 and VP4. VP1, VP2, and VP3 form the major part of the protein capsid. The much smaller VP4 protein has a more extended structure, and lies at interface between the capsid and the RNA genome. There are 60 copies of each of these proteins assembled as an icosahedron. Antibodies are a major defense against infection with the epitopes lying on the exterior regions of VP1-VP3.

Rhinovirus Transmission and Epidemiology

There are two modes of transmission: via aerosols of respiratory droplets and from contaminated surfaces, including direct person-to-person contact. A high majority of colds are transmitted by autoinoculation by contact with contaminated surfaces.

Rhinovira occur worldwide and are the primary cause of common colds. Symptoms include sore throat, runny nose, nasal congestion, sneezing and cough; sometimes accompanied by muscle aches, fatigue, malaise, headache, muscle weakness, or loss of appetite. Fever and extreme exhaustion are more usual in influenza. Children may have six to twelve colds a year. In the United States, the incidence of colds is higher in the fall and winter, with most infections occurring between September to April. The seasonality may be due to the start of the school year, or due to people spending more time indoors (thus in closer proximity with each other), increasing the chance of transmission of the virus.

Rhinovirus Pathogenesis

The primary route of entry for rhinovira is the upper respiratory tract. Afterward, the virus binds to ICAM-1 (Inter-Cellular Adhesion Molecule 1) also known as CD54 (Cluster of Differentiation 54) receptors on respiratory epithelial cells. As the virus replicates and spreads, infected cells release distress signals known as chemokines and cytokines (which in turn activate inflammatory mediators).

Infection occurs rapidly, with the virus adhering to surface receptors within 15 minutes of entering the respiratory tract. Just over 50% of symptomatic individuals will experience symptoms within 2 days of infection. Only about 5% of cases will have an incubation period of less than 20 hours, and, on the other end, it is expected that 5% of cases would have an incubation period of greater than four and a half days.

Rhinovira preferentially grow at 32°C as opposed to 37°C, hence infect the upper respiratory tract.

Rhinovirus Novel Antiviral Drugs

Interferon-alpha used intranasally was shown to be effective against rhinovirus infections. However, volunteers treated with this drug experienced some side effects, such as nasal bleeding, and began developing resistance to the drug. Subsequently, research into the treatment was abandoned.

Pleconaril is an orally bioavailable antiviral drug being developed for the treatment of infections caused by picornaviruses. This drug acts by binding to a hydrophobic pocket in VP1, and stabilizes the protein capsid to such an extent that the virus cannot release its RNA genome into the target cell. When tested in volunteers, during the clinical trials, this drug caused a significant decrease in mucus secretions and illness-associated symptoms. Pleconaril is not currently available for treatment of rhinoviral infections, as its efficacy in treating these infections is under further evaluation.

There are potentially other substances such as Iota-Carrageenan that may lead to the creation of drugs to combat the rhinovirus.

Rhinovirus Vaccine

There are no vaccines against these vira as there is little-to-no cross-protection between serotypes. At least 99 serotypes of rhinoviruses affecting humans have been sequenced.

However, recent study of the VP4 protein has shown it to be highly conserved amongst many serotypes of Rhinovirus, opening up the potential for a future pan-serotype Rhinovirus vaccine.

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