A Home For The Common Cold

1 December 2012 by Nsikan Akpan, posted in TBS Journal Club

Autumn is “the season of sniffles”, especially here in Brooklyn. Once the temperature drops, I can’t help but notice all the coughs and sneezes that start emanating thru the early-morning din of my subway commute. Most of them are probably suffering from a common cold and will do so a handful of times throughout the year1.

But have you ever wondered: if the common cold is so…common, why hasn’t a cure been found?

Blame should be heaped upon rhinoviruses (the #1 cause of the common cold) and a seemingly simple task that has proved difficult for scientists: growing these microbes in a petri dish.

Known as “viral culturing”2, this technique has been crucial for developing vaccines for serious pandemics, such as for polio and hepatitis A/B.

Two groups—one from Wisconsin, the other from Maryland—claim to have cracked the “culture barrier” for a very dangerous type of rhinovirus, and their discovery could also be the key to finding a vaccine for the common cold.


3 Little Rhinos

Human rhinoviruses (HRVs) are amongst the smallest pathogens found in nature, but belong to a very diverse family, with 100+ members being classified into 3 species (HRV-A, -B, and -C). While the ‘As’ and ‘Bs’ have been studied extensively since the 1950s, little is known about HRV-C, whose existence only came to light 5-6 years ago.

Despite its recent discovery, HRV-C might be the most harmful of the 3 species. Multiple reports have linked HRV-C to severe respiratory conditions, like bronchitis, and two large studies of children with asthma3 showed that HRV-C infection elevated one’s likelihood of having an asthma attack.


Raising Arizona HRV-C

Research on HRV-C has been stifled by a collective inability to cultivate the virus in a lab. This is usually accomplished by growing cells that are susceptible to the virus in a petri dish, and then adding the virus to the culture dish. The virus infects and spreads amongst the cells, and thus the cells function as a virus breeding ground.

In humans, rhinoviruses infect the cells that coat our nose, throat, and lungs. This lining is mainly comprised of epithelial cells.

For decades, HeLa cellsof Henrietta Lacks infamy—have been used to culture HRV-A and HRV-B, but this epithelial cell line has never worked for HRV-C4.

As an alternative, Yury Bochkov and James Gern of the University of Wisconsin decided to go straight to the source.  They took tissue from human nasal sinuses—leftover from surgical biopsies—and grew it in a petri dish with HRV-C. When they returned to the lab a few days later, lo’ and behold! They had found a culture system for HRV-C.

Not too earthshattering, given they essentially moved the natural context for HRV-C—the human nose—into a lab incubator. Plus tissue biopsies can be hard to come by because they are dependent upon patient compliance and availability

Arguably a more utilitarian discovery is reported in this month’s Journal of Virology, where scientists at the biotech company MedImmune established a similar system but with commercially available epithelial cells5. MedImmune’s system relinquishes the hurdle of finding fresh human airway tissue.


A World Without Colds.

After reading these studies, I couldn’t help but feel a tad hopeful. A toddler sneezed on my train ride home—his nose probably stuffed with rhinoviruses—and I thought Worry not, young one. The future is nigh.

Previous attempts at a rhinovirus vaccine are now suspected to have failed because they targeted HRV-A and HRV-B, but neglected HRV-C.

Although there is still much left to do before an HRV-C vaccine is available, these findings provide a preliminary arena for answering some major questions. Which cell receptor(s) does HRV-C use to infiltrate the body? Why is it more damaging than its cousins HRV-A and HRV-B?

But as I stared at this child’s rosy nose, another question came to mind: do we want a world without rhinoviruses?

Humans, wildlife, and livestock are constantly facing the consequences of excessive antibiotic use (MRSA and drug-resistant TB). It is possible that early rhinovirus vaccines floundered because these viruses rapidly evolved drug resistance. Plus rhinoviruses aren’t the only ‘bugs’ that causes the common cold. Could coronaviruses, already responsible 10-15% of colds, or some other infection become the new champion of the stuffy nose?

Rather than fill my head with more speculation/paranoia, I offered the kid’s mom a Kleenex and washed my hands when I got home.

Geek Notes (for the scientists):                               

1a handful of times throughout the yearOn average, infants have 6–8 colds each year, and the incidence declines into adulthood, where people typically suffer from 2–4 colds per year.

2Known as “viral culturing”…I am mainly referring to cultivating viruses in a cell monolayer, but viruses can also be raised in avian embryos a.k.a. chicken eggs.

4has never worked for HRV-C…HRV-C also fails to grow in other epithelial cell lines. A mouse model does exists for HRV-A/B.

5commercially available epithelial cells…Classic mammalian cell culture requires covering a monolayer of cells in a petri dish with growth media—a physiological salt solution filled with nutrients for the cells to thrive. But an alternate technique can be used for nasal and lung epithelial cells, known as the air-liquid interface method. Rather than completely submerge the cells, they are partially soaked in a thin layer of growth media but also partially exposed to the air. This mimics the context of the lungs, which are just damp, airy sacs. Bronchial epithelial cells grown in this manner form cilia, produce mucus, and express a gene profile that is similar to the in vivo scenario.

The Papers

Bochkov YA, Palmenberg AC, Lee WM, Rathe JA, Amineva SP, Sun X, Pasic TR, Jarjour NN, Liggett SB, & Gern JE (2011). Molecular modeling, organ culture and reverse genetics for a newly identified human rhinovirus C. Nature medicine, 17 (5), 627-32 PMID: 21483405

Hao W, Bernard K, Patel N, Ulbrandt N, Feng H, Svabek C, Wilson S, Stracener C, Wang K, Suzich J, Blair W, & Zhu Q (2012). Infection and propagation of human rhinovirus C in human airway epithelial cells. Journal of virology, 86 (24), 13524-32 PMID: 23035218

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