Rhinoviruses are transmitted through aerosols, respiratory droplets, fomites, and direct person-to-person contact.[2] They primarily infect nasal epithelial cells in the airway and cause mild symptoms such as sore throat, cough, and nasal congestion.[3][4] However, rhinovirus infection can cause more severe disease in infants, the elderly, and the immunocompromised. Rhinoviruses are also recognized as a major cause of asthma exacerbations.[5]
As of December 2023, there are no FDA-approved vaccines or antiviral treatments for rhinovirus infection.[4]
History
In 1953, when a cluster of nurses developed a mild respiratory illness, Winston Price, from the Johns Hopkins University, took nasal passage samples and isolated the first rhinovirus, which he called the JH virus, named after Johns Hopkins.[6][7] His findings were published in 1956.[8]
In 2006, advancements in molecular testing techniques for identifying rhinoviruses in clinical specimens led to the discovery of rhinovirus C species in samples from Queensland, Australia and New York City, United States. The ICTV formally designated RV-C as a separate species in 2009.[3]
Rhinoviruses can survive on surfaces such as stainless steel or plastic for several hours.
Airborne precautions[9] are likely effective in reducing transmission, while other precautions such as hand-washing or cleaning surfaces with disinfectants are known effective in preventing rhinovirus transmission.[10]
Signs and symptoms
Main article:
exhaustion are less common in rhinovirus infection compared to influenza
.
Epidemiology
Rhinoviruses can be detected year-round; however, the incidence of rhinovirus is higher in the autumn and winter, with most infections occurring between September and April.[11] The seasonality may be due to the start of the school year and to people spending more time indoors thereby increasing the chance of transmission of the virus.[12] Lower ambient temperatures, especially outdoors, may also be a factor given that rhinoviruses preferentially replicate at 33 °C (91.4 °F) as opposed to 37 °C (98.6 °F).[11][13] Other climate factors such as humidity may influence rhinovirus seasonality.[11] Young children (<5 years old) experience a high rate of infection which can be detected in community surveillance studies of children up to 34% of the year.[14]
Those most affected by rhinoviruses are infants, the elderly, and
The primary route of entry for human rhinoviruses is the upper
CD54 (Cluster of Differentiation 54), on respiratory epithelial cells, as receptors to bind to. Some subgroups under A and B uses the "minor" LDL receptor instead.[15] Rhinovirus C uses cadherin-related family member 3 (CDHR3) to mediate cellular entry.[16] 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 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, at the other extreme, it is expected that 5% of cases would have an incubation period of greater than four and a half days.[17]
Human rhinoviruses preferentially grow at 33 °C (91.4 °F), notably colder than the average human body temperature of 37 °C (98.6 °F), hence the virus's tendency to infect the
upper respiratory tract, where respiratory airflow is in continual contact with the (colder) extrasomatic environment.[11][13]
Rhinovirus A and C species viruses are more strongly associated with significant illness and wheezing, while rhinovirus B species are more commonly mild or asymptomatic.[3][18]
Taxonomy
Rhinovirus was formerly classified as a genus of the family Picornaviridae. The 39th Executive Committee (EC39) of the International Committee on Taxonomy of Viruses (ICTV) met in Canada during June 2007 with new taxonomic proposals. In April 2008, the International Committee on Taxonomy of Viruses voted and ratified the following changes:[20]
2005.264V.04 To remove the following species from the existing genus Rhinovirus in the family Picornaviridae:
Human rhinovirus A
Human rhinovirus B
2005.265V.04 To assign the following species to the genus Enterovirus in the family Picornaviridae:
Human rhinovirus A
Human rhinovirus B
2005.266V.04 To remove the existing genusRhinovirus from the family Picornaviridae. Note: The genus Rhinovirus hereby disappears.
The merge is based on the grounds that the two "genera" of viruses are not significantly different in a virological sense. They have identical genome organizations and particle structures, and the phylogeny is not always monophyletic.[21]
In July 2009, the ICTV voted and ratified a proposal to add a third species, Human rhinovirus C to the genus Enterovirus.[22]
2008.084V.A.HRV-C-Sp 2008.084V To create a new species named Human rhinovirus C in the genus Enterovirus, family Picornaviridae.
There have been a total of 215 taxonomic proposals, which have been approved and ratified since the 8th ICTV Report of 2005.
Types
Prior to 2020, enteroviruses (including all rhinoviruses) were categorized according to their serotype. In 2020 the ICTV ratified a proposal[21] to classify all new types based on the genetic diversity of their VP1 gene.
Human rhinovirus type names are of the form RV-Xn where X is the rhinovirus species (A, B, or C) and n is an index number. Species A and B have used the same index up to number 100, while species C has always used a separate index. Valid index numbers are as follows:[1]
There are currently no FDA-approved antiviral drugs to treat rhinovirus infections.[4] Several novel antiviral compounds have been tested in clinical trials without sufficient efficacy to progress to FDA approval. Compounds specifically targeted for rhinoviruses, or more broadly, picornaviruses, include the following:
Rupintrivir is a peptidomimetic drug developed for treatment of rhinovirus infections.[26] Rupintrivir inhibits human rhinovirus 3Cprotease and prevents cleavage of the rhinovirus polyprotein following translation, therefore preventing viral assembly and replication. A phase II clinical trial of rupintrivir using experimentally induced rhinovirus infection in healthy volunteers demonstrated efficacy in reducing viral load and symptom severity. However, further trials testing rupintrivir in treating natural infections showed minimal benefit, and further clinical development was halted.[27]
picornaviruses.[28] 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. Phase III clinical trials showed a slight reduction in symptom duration if taken within 24 hours of symptom onset.[29][30] However, the FDA denied approval of pleconaril due to concerns about side effects, limited efficacy in non-white participants, and difficulty in treating most patients within a 24 hour window.[31][32]
Other treatments aiming to reduce rhinovirus infection symptoms include immunomodulatory agents. These may promote beneficial antiviral responses or reduce inflammatory responses associated with symptoms. Interferon-alpha used intranasally was shown to be effective against human rhinovirus infections. However, volunteers treated with this drug experienced some side effects, such as nasal bleeding and began developing tolerance to the drug. Subsequently, research into the treatment was abandoned.[33] Inhaled budesonide has been shown to reduce viral load and pro-inflammatory IL-1β in mice. Omalizumab, which was developed for treatment of severe allergic asthma, has shown evidence in reducing symptom severity of asthma patients infected with rhinovirus.[27]
Vaccine development
There are no vaccines against these viruses as there is little-to-no cross-protection between serotypes. At least 165 types of human rhinoviruses are known.[1] However, a study of the VP4 protein has shown it to be highly conserved among many serotypes of human rhinovirus, opening up the potential for a future pan-serotype human rhinovirus vaccine.[34] A similar result was obtained with the VP1 protein. Like VP4, VP1 also occasionally "pokes" out of the viral particle, making it available to neutralizing antibodies. Both peptides have been tested on rabbits, resulting in successful generation of cross-serotype antibodies.[35]
Rhinovirus genome has a high rate of variability in human circulation, even occurring with genomic sequences that differ up to 30%.[36] Recent studies have identified conserved regions of the rhinovirus genome; this, along with an adjuvanted polyvalent rhinovirus vaccine, shows potential for future development in vaccine treatment.[37]
Human rhinovirus can remain infectious for up to three hours outside of a human host. Once the virus is contracted, a person is most contagious within the first three days. Preventative measures such as regular vigorous handwashing with soap and water may aid in avoiding infection. Avoiding touching the mouth, eyes, and nose (the most common entry points for rhinovirus) may also assist prevention. Droplet precautions, which take the form of a surgical mask and gloves, are the method used in major hospitals.[38] As with all respiratory pathogens once presumed to transmit via respiratory droplets, it is highly likely to be carried by the aerosols generated during routine breathing, talking, and even singing. In order to prevent airborne transmission, droplet precautions are insufficient, and routine airborne precautions are necessary.[39]