The `M' Word

 


#10,865



If you want to draw your reader's attention to an infectious disease story, including the `M' word - `Mutation' - in the headline is a surefire technique. For most people, the `M' word evokes a sense of dread - a belief that something `bad' has happened.

A concept, I suspect, that has been fostered by scores of grade-B Sci-Fi movies over the past 60 years that always seem to use `mutations' as the genesis of their `monsters'. 

The truth is, viruses are constantly mutating.  It's what they do.  It's part of the evolutionary process.  RNA viruses - like influenza and MERS - are particularly prone to `duplication errors' during replication, and are constantly introducing mutations.


Most are of little consequence, and do nothing to affect transmissibility, replication, host range, or virulence. Some prove detrimental, making the virus less `fit' than its predecessors, and they end up as evolutionary failures. 

Only rarely does a mutation enhance a virus in a way to make it deadlier, more transmissible, or a greater threat. 

That isn't to say it doesn't ever happen.   A few examples include:

• A mutation in the envelope protein gene (E1-A226V) of the CHKV virus allowed Aedes Albopictus or `Asian tiger’ mosquito to transmit the virus more efficiently (see A Single Mutation in Chikungunya Virus Affects Vector Specificity and Epidemic Potential).
• The H275Y mutation in seasonal H1N1 back in 2007-2008 pretty much negated the effectiveness of NAI (Neuraminidase Inhibiting) antiviral drugs (see CIDRAP article With H1N1 resistance, CDC changes advice on flu drugs). Luckily that virus was supplanted by the 2009 H1N1 virus, which remains susceptible the drug.
• And for avian flu, researchers have determined the (E627K) substitution in the (PB2) protein makes the an influenza virus better able to replicate at the lower temperatures (roughly 33C) normally found in the upper human respiratory tract (see Eurosurveillance: Genetic Analysis Of Novel H7N9 Virus).

But when a new mutation is observed, scientists rarely know immediately what effects it will have on a virus. Determining that can take months of observation and research.   Complicating matters, mutations don't happen in a vacuum.

Changes often occur in multiple regions of the virus simultaneously, and different combinations may yield different outcomes.

Last summer, during the height of Korea's MERS outbreak, initial reports stated that the Korean MERS Sequences Closely Match Middle Eastern Virus. `Closely' isn't the same as `exactly', of course, and figuring out what - if any - impact minor changes might have isn't easy.


Overnight the Korean and International press is filled with reports announcing a `mutation' in the Korean MERS strain, and that it may have contributed to the virus's rapid spread.

Mutation found in MERS virus in Korea

By Kim Se-jeong

The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) which swept Korea last year underwent a mutation not found in the strains of MERs samples collected in Saudi Arabia, according to the Korea Centers for Disease Control and Prevention (KCDC), Friday.

The mutation may have affected the virulence of the virus as it has shown different patterns of spreading and infection in Korea from those in Saudi Arabia, such as an unusually fast human-to-human transmission.

While investigators suspected a mutation at the time of the epidemic, health authorities denied it.

This is the first official confirmation of the mutation.

(Continue . . . )

Showing some restraint, this article only used the word `mutation' 7 times (counting the headline).   Sparking all this ballyhoo is a dispatch, appearing in the EID journal, which finds:

Volume 22, Number 1—January 2016

Dispatch

Variations in Spike Glycoprotein Gene of MERS-CoV, South Korea, 2015

Dae-Won Kim¹, You-Jin Kim¹, Sung Han Park, Mi-Ran Yun, Jeong-Sun Yang, Hae Ji Kang, Young Woo Han, Han Saem Lee, Heui Man Kim, Hak Kim, A-Reum Kim, Deok Rim Heo, Su Jin Kim, Jun Ho Jeon, Deokbum Park, Joo Ae Kim, Hyang-Min Cheong, Jeong-Gu Nam, Kisoon Kim, and Sung Soon Kim 

Author affiliations: Korea Centers for Disease Control and Prevention, Cheongju-si, South Korea

Suggested citation for this article

Abstract

An outbreak of nosocomial infections with Middle East respiratory syndrome coronavirus occurred in South Korea in May 2015. Spike glycoprotein genes of virus strains from South Korea were closely related to those of strains from Riyadh, Saudi Arabia. However, virus strains from South Korea showed strain-specific variations.

(SNIP)

Conclusions

Accurate genome sequencing can identify spatiotemporal patterns that help understand dynamics of rapid spread of MERS-CoV infection. We report S glycoprotein gene sequences of MERS-CoV from 8 patients and a strain cultured in Vero cells. Genetic information obtained is useful for understanding the evolutionary history of MERS-CoV.

On the basis of our phylogenetic analyses, virus sequences of strains isolated in South Korea in 2015 form a unique clade. Genetic variations elucidated in this study show an unreported sequence in the RBD, which suggests that MERS-CoV circulating in South Korea during the outbreak in 2015 has higher genetic variability and mutation rates. However, we cannot conclude that deleterious effects promoting spread of infection will occur because of these mutations. Additional genetic information will resolve precise characteristics of the MERS-CoV obtained during the outbreak in South Korea.

(Continue . . .)

In other words, researchers found enough genetic variance among the small subset of the Korean viruses they sequenced to place them into a new clade. Two mutations were in the receptor binding domain of the virus's spike protein.

Interesting, but their significance is far from clear. 

To determine that may take months, or even years. By the time we know what they mean, additional changes to the virus may have rendered the point moot. Or not.  We'll see.

But at least for now, the ability to invoke the  `M' word in headlines will probably sell a lot of newspapers. 

Dr. Ian Mackay on his VDU blog this morning goes into more detail on Korean MERS research, and these reported changes to the virus.  Follow the link below to read:

Research on MERS in South Korea seems fractured...