Human Rhinovirus

We’ve all been plagued by it at one point or another, and while we’ve not known the name for it, we will now – the human rhinovirus (HRV), also known as the “common cold”. While not all common colds are caused by the rhinovirus, over 50% are, making it the most prevalent infection keeping you and me out of school, work, and any other obligations [1]. So, what gives? Why is this infection so prominent, what is it, exactly? How does it impact us, diagnostically, cellularly? That is what we are here to find out, and more.

What is Human Rhinovirus?

Human Rhinovirus (HRV) is, as the name says, a viral infection known to cause over 50% of common colds across the world [1][2]. This virus is spherical in shape and comes in 3 main forms (with more genetic variations within each isoform): HRV-A, HRV-B, HRV-C [9].

How does it present - diagnostically?

Rhinovirus presents by infecting the upper section of the respiratory system, causing middle ear infection (most common in children), and sinus infection; however, recent evidence has shown rhinovirus to infect the lower respiratory tract, as well [1][2]. Symptoms will include sore throat, runny nose, coughing, sneezing, and body aches [5].

The upper section is made up of the nose, throat, pharynx, larynx, and bronchi [4]. The lower section is made up of the trachea, and the lungs (bronchioles, alveoli, etc.) [3]. These areas will simply be irritated, partially blocked, and will secrete mucus [6].


Can HRV be asymptomatic?

Yes, HRV can, in some cases, show no symptoms – this is most commonly seen in children.

Conditions of Life?

Human rhinovirus grows within a range of 31 – 35℃ (89 - 95℉), but thrives in 33℃ [1]. Rhinovirus can be found anywhere in the world and is not specific to any particular place.

Level of Danger?

This is difficult to say, because while the rhinovirus will often come and go, the true indication of danger is the starting condition of the host. In most cases, rhinovirus is harmless, other than being an irritant for some time, but in some cases – especially those with asthma, pneumonia, cystic fibrosis, chronic obstructive pulmonary disease, bronchitis, and anyone immunocompromised (AIDS, possibly elderly, possibly babies), rhinovirus can lead to increasingly severe consequences [1][2][7][8]. While there are no documented cases (to my knowledge) of HRV killing anyone directly, HRV has led to 40% of those with HRV respiratory symptoms to be admitted by a hospital, 11% to be admitted in intensive care, and 3% died (2 patients, of those admitted) from HRV complications [2]. However, to be clear, it was not rhinovirus alone that killed these patients, it was a combination of illnesses (like the ones listed above) plus the added stress of HRV presence leading to the rare death.

Transmission?

The most common means of transmission is through touching with the hands/fingers to the eye and nose, because the quantity transmitted is around 300 TCID50/ml (TCID, or Tissue Culture Infective Dose), as opposed to inhalation or kissing which would transmit via saliva, but only transmit around 10 TCID50/ml [7].

Duration?

Duration of the virus is dependent on immune response, but tends to be around 7 – 10 days (can last weeks) [5][13]. The final symptom is, typically, a cough in adults and congestion in children [7].

Understanding the Pathophysiology

As we know, human rhinovirus comes in a icosahedral shape with the shape created by a protein shell housing RNA genome [9]. This capsule/protein is made up of several interlinked polypeptides [9][10]. So, after the transmission of the virus to the host (you), the virus attaches to particular receptors on a variety of cells [10]. In 90% of HRV-A and HRV-B, the attachment is at a receptor known as Intercellular Adhesion Molecule – 1 (ICAM-1) [10][11]. Now, ICAM-1 is not around in plentiful amounts unless stimulated by cytokines released from immune cells that then use ICAM-1 to attach and migrate within tissues [11]. On the other hand, little is known about HRV-C’s entry into the cell [10]. However, ICAM-1 is not the only way by which viruses find their way into the cells. These viruses can also use low density lipoprotein receptors, and even some uncharacterized binding sites, as well as break into the cytoplasm by creating holes or viral receptors [11][14].

Pictured, the virion finds its way into the cell via 3 different methods; the primary, through ICAM-1, the secondary via LDL Receptor, and the third not being known.

Rhinoviruses then tend to concentrate around the receptor of choice and as they transmigrate into the cell, they shed their protein casing – typically via disassembling sections of the cell membrane that pick apart the casing to then expose the viral RNA upon the cell’s cytoplasm [11]. Once the virus enters the cell via endocytosis and its shell has been removed, the RNA within the capsule acts as mRNA of the cell and is translated through the cell’s ribosomes into polypeptides [2][12]. These polypeptides are then used to create viral proteins which further act on the cell, and although unclear how, tend to find a way to prioritize ribosome activity of viral RNA [12]. The virus then sheds to other cells [13][14].

Interestingly, although the rhinovirus does tend to infect epithelial cells of the respiratory system, there is little evidence that the infection is widespread; meaning, the virus is strangely absent in a majority of the cells and may not have a direct damaging impact, so it may be possible that the immune response is the only physical tell of viral infection, not the infection itself [13]. This may also be the reason for why the virus can be asymptomatic in some individuals, especially children (with a higher trend of asymptomatic individuals the younger the age); although, this may be due to communication barriers or it could very well be due to an underdeveloped or overactive, chronic immune system, or another reason altogether [2]!

Understanding the Immunity Physiology

The object of the articles, however, is not to simply inform us of the bad, but to capture our fascination in how amazing our body is, and as such, let us get into some of the intricate defense systems our body employs.

So, as the human rhinovirus attaches to various receptors around the cell’s membrane (some are found within the cell), there are yet other receptors that are specialized in detecting foreign bodies [2][15]. Still, it does not do the process justice to say they detect foreign bodies; more specifically, pathogens (and other non-host, read: anything not “you”) release trace molecules and these trace molecules, called Pathogen Associated Molecule Patterns (PAMPs), are then identified by these specialized receptors called Pattern Recognition Receptors (PRR) [15]. A specific family of PRR, by the name of Toll-like Receptors (TLRs), use varying recognition patterns; the first being a simple recognition pattern as these receptors do not recognize any host molecules, so anything noticed effectively triggers a response, and the second, being more specialized as each receptor can identify specific pathogens based on the order and type of molecules released by the pathogen [15][16].

Once these receptors notice foreign molecules or a foreign arrangement of molecules, then they lead to a release of pro-inflammatory markers [2][16]. These markers are called cytokines, or more specific to the situation, they are called chemokines, and allow for the infected cell to communicate to other cells [2]. The release of cyto/chemo-kines like interleukin-6 (IL-6), interleukin-8 (IL-8), interferon, and a variety of other ligands and chemokines ends up communicating to specific immune cells to draw closer to the area [2].

Here, you see Toll-like Receptors on the outside and inside of the cell recognizing the invasion of the HRV, which leads to the release of signals (IL-6, IFN, etc.) to the rest of the body to send immune cells to destroy the virus, as well as the infected cell. 

Immune cells, such as T-cells, B-cells, and polymorphonuclear (PMN) cells (white blood cells) then attack the cell and destroy it to rid the virus as the virus needs a live host to replicate its RNA, and without the newly entered cell, it can no longer shed to other cells (although, as we’ve discussed, HRV does not shed readily) [2].

After the few days or weeks in which the immune system has rid the body of the virus, the B-cells begin to secrete antibodies to the specific expression of human rhinovirus, leading to a virtual immunity from further infection [17]. I say “virtual”, because it is, technically, possible to be infected by the exact same virus again, but the immune system has a specialized antibody that has been specially synthesized for just such an occasion, so T-cells become especially effective to the reentry of the virion and can signal and destroy the infection at an accelerated rate compared to before [2][17][18]. This process essentially cements a type of immunity from the specific iteration of the human rhinovirus, but not from other versions of the same virus.

Cure/Treatment?

There is no cure for the human rhinovirus, because it is a virus, it is extremely common, and is non-life threatening, so there is little reason to focus resources to curing it. That said, there are some anti-viral drugs that may be effective at helping the immune system stress and discourage further HRV infection, but again, since HRV is non-life threatening, it seems nonsensical to go a route of that sort. Zinc supplementation, however, by lozenge or by syrup administration seems to decrease the duration of rhinovirus [2][20][21]. It should be, briefly, noted that zinc intake may lead to nausea and a few other minor side effects [22]. It has been postulated that zinc has a particular physical shape that fits in the virus’ binding sites, essentially blocking it from attaching to cells – but the mechanism has not been elucidated [21].

SUMMARY

It is difficult to summarize such a complex topic, but a few of the highlights are that human rhinovirus is the main cause of the common cold, it presents no danger of death on its own, but can have an additive effect if other illnesses are involved. The most common transmission is through touch to the eyes and nose, and the illness tends to stick around for 7-10 days. There is no cure, and other than antiviral medication (which is unlikely to be an option for such a benign condition), there is also zinc lozenges which have been shown to reduce the duration of more serious infections.

Writer: Nicolas Verhoeven
References

[1] Turner, R. (2007). Rhinovirus: More than Just a Common Cold Virus. The Journal of Infectious Diseases, 195(6), 765-766. doi:10.1086/511829

[2] Jacobs, S. E. (2013). Human Rhinoviruses. Clinical Microbiology Revier, 26(1), 135-162. Retrieved from https://dx.doi.org/10.1128%2FCMR.00077-12

[3] Mannheim, J. K. (2016). Lower respiratory tract: MedlinePlus Medical Encyclopedia Image. Retrieved from U.S. National Library of Medicine website: https://medlineplus.gov/ency/imagepages/19379.htm

[4] Acute Upper Respiratory Infection. (n.d.). Retrieved from http://www.healthline.com/health/acute-upper-respiratory-infection#Treatment7

[5] Common Colds: Protect Yourself and Others | Features | CDC. (2017). Retrieved from Center of Disease Control website: https://www.cdc.gov/features/rhinoviruses/

[6] Treating acute sinusitis - National Library of Medicine - PubMed Health. (2015). Retrieved from U.S. National Library of Medicine website: https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0072667/

[7] Winther, B. (2011). Rhinovirus Infections in the Upper Airway. Proceedings of the American Thoracic Society, 8(1), 79-89. doi:10.1513/pats.201006-039rn

[8] Papadopoulos, N. (2001). The rhinovirus--not such an innocent? QJM, 94(1), 1-3. doi:10.1093/qjmed/94.1.1

[9] Kennedy, J. L. (2012). Pathogenesis of Rhinovirus Infection. Curr Opin Virology, 2(3), 287-293. Retrieved from https://dx.doi.org/10.1016%2Fj.coviro.2012.03.008

[10] Bella, J., & Rossmann, M. G. (2000). ICAM-1 receptors and cold viruses. Pharmaceutica Acta Helvetiae, 74(2-3), 291-297. doi:10.1016/s0031-6865(99)00056-4

[11] Long, E. O. (2011). Intercellular Adhesion Molecule 1 (ICAM-1): Getting a Grip on Leukocyte Adhesion. Journal of Immunology, 186(9). Retrieved from https://dx.doi.org/10.4049%2Fjimmunol.1100646

[12] Gamarnik, A. V., Boddeker, N., & Andino, R. (2000). Translation and Replication of Human Rhinovirus Type 14 and Mengovirus in Xenopus Oocytes. Journal of Virology, 74(24), 11983-11987. doi:10.1128/jvi.74.24.11983-11987.2000

[13] Hay, C. M. (n.d.). THE RESPIRATORY VIRUSES: INFLUENZA, RSV, AND RHINOVIRUSES. Retrieved from http://www.columbia.edu/itc/hs/medical/pathophys/id/2008/respiratoryvirusesNotes.pdf

[14] Blaas, D., & Fuchs, R. (2016). Mechanism of human rhinovirus infections. Molecular and Cellular Pediatrics, 3(1). doi:10.1186/s40348-016-0049-3

[15] Medzhitov, R. (2001). Toll-like receptors and innate immunity. Nature Reviews Immunology, 1, 135-145. Retrieved from http://www.nature.com/nri/journal/v1/n2/full/nri1101-135a.html

[16] Triantafilou, K., Vakakis, E., Richer, E. A., Evans, G. L., Villiers, J. P., & Triantafilou, M. (2011). Human rhinovirus recognition in non-immune cells is mediated byToll-like receptors and MDA-5, which trigger a synergetic pro-inflammatory immune response. Virulence, 2(1), 22-29. doi:10.4161/viru.2.1.13807

[17] Alberts, B. (2002). B Cells and Antibodies. In Molecular Biology of the Cell (4th ed.). Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK26884/

[18] The defense mechanisms of the adaptive immune system. (2016). Retrieved from U.S. National Library of Medicine website: https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0072581/

[19] Zinc — Health Professional Fact Sheet. (n.d.). Retrieved from https://ods.od.nih.gov/factsheets/Zinc-HealthProfessional/

[20] Hulisz, D. (2004). Efficacy of Zinc Against Common Cold Viruses: An Overview. Journal of the American Pharmacists Association, 44(5), 594-603. doi:10.1331/1544-3191.44.5.594.hulisz

[21] Novick, S., Godfrey, J., Godfrey, N., & Wilder, H. (1996). How does zinc modify the common cold? Clinical observations and implications regarding mechanisms of action. Medical Hypotheses, 46(3), 295-302. doi:10.1016/s0306-9877(96)90259-5

[22] Science, M., Johnstone, J., Roth, D. E., Guyatt, G., & Loeb, M. (2012). Zinc for the treatment of the common cold: a systematic review and meta-analysis of randomized controlled trials. Canadian Medical Association Journal, 184(10), E551-E561. doi:10.1503/cmaj.111990

Pictured, the virion finds its way into the cell via 3 different methods; the primary, through ICAM-1, the secondary via LDL Receptor, and the third not being known.

"CLICK" for Most Recent