Influenza virion
Influenza virion

At this point in 2009, I think most people probably have a general grasp of influenza virus infection patterns.  At the simplest level, a few strains of virus circulate every year, with relatively small changes year-to-year.  Every so often, a new strain, with larger changes, appears and spreads globally, often becoming the dominant “base” strain for a while (that is, circulating annually with smallish changes each year) until it in turn is replaced by a new strain.

A particularly interesting “new” influenza strain appeared in 1977.  At that time the dominant circulating strains didn’t include any H1N1 strains; H1N1 had gone extinct in humans around 1957. (H1N1 was still circulating in swine, though.) An H3N2 strain, the tail end of the 1968 pandemic influenza, was the major strain. 1 But in 1977, H1N1 returned, first isolated in China and subsequently in Russia, then rapidly spreading throughout the world and remaining endemic since then, circulating in parallel with H3N2 strains since then.  (That’s why influenza vaccines are trivalent — they cover both an H1N1 and an H3N2 strain of influenza A, plus an influenza B strain.)

It was quickly discovered that the “new” H1N1 was not new at all.  Even without modern genomic sequencing systems, Peter Palese’s group was able to show that the 1977 H1N1 was actually an old strain,2 described in 1950, that had re-appeared without any evidence of evolution throughout the dozen intervening years. Although Palese didn’t outright say it at the time, this almost certainly was a laboratory strain of influenza that had escaped back into the wild.

Finally, it is possible that a 1950 influenza virus was truly frozen in nature or elsewhere and that such a strain was only recently reintroduced into man. 2

(My emphasis.)

Influenza signA couple of side notes before I continue.  There are several other claims in the literature that various influenzas since 1977 are lab escapees.  Most, if not all, of those claims are almost certainly wrong, and represent a different kind of lab contamination — reference strains of influenza that have contaminated the test strain, within the lab, rather than a lab strain actually circulating in the wild. 3 This form of lab contamination with reference strains seems to be a relatively common source of error,4 and it’s certainly a problem, but isn’t an actual direct threat to the population.

In particular, the swine-origin H1N1 is not a lab escapee (and, in spite of the rumors among bloggers who don’t know anything about viruses, but who dearly love a conspiracy theory, it’s not an artificial construct).  Although the details of the SOIV origins are fuzzy, its parents and family tree is pretty clear by now.

That said, lab escapes are not unheard of.  Notoriously, the last case of smallpox was a lab escape, and the 2007 outbreak of foot and mouth disease in the UK was almost certainly an escaped lab strain from the Pirbright Research Center. 5 The problem with the conspiracy theories6 isn’t that virologists say lab escape is impossible.  We know perfectly well that lab escapes can, and do, happen.  The reason the conspiracy theories are wrong is that escapes have happened and been promptly detected and reported.  There’s no conspiracy.

Dengue virus
Dengue virus

What may be the latest example of this was just reported in PLoS One.7  In the course of analyzing Dengue virus strains circulating in Brazil and Columbia, an unexpected strain was detected: It is a strain that was present in Asia some 20 years ago, almost unchanged since.  Like influenza, dengue viruses mutate and evolve fairly rapidly; this kind of stability (35-fold lower than expected) would be extraordinary in a virus that’s been circulating for two decades.  What’s more, these viruses don’t show geographic clustering. Normally, dengue viruses circulate locally and develop local sub-strains; this older virus, though, is very similar in Brazil and Columbia, and doesn’t group with local viruses:

DENV-3, when introduced to a new area, evolves locally, resulting in geographically-associated clusters closely related to other virus recently circulating in other region.  Interestingly, we have shown in this study that viruses recently circulating in Brazil and Colombia form a monophyletic cluster together with viruses isolated in Asia more than two decades ago.7

There are two obvious possible explanations.  One is that this represents lab error — the strains they were analyzing were somehow contaminated with this older strain.  The other is that this is a lab escapee:

Could some how this strain escape from the laboratory and started to infect humans, thus explain the close relationship of the new viruses with genotype V strains?7

I’d like to see this work repeated by an independent lab to make sure it’s not lab contamination (and the authors clearly want the same thing: “Therefore, more studies are needed to confirm the origin of American genotype V viruses”) but it certainly seems like a plausible explanation.

I’m not a Dengue expert by any means, but I don’t think there’s anything especially hazardous about the “new” (old) strain — Dengue is already widely present in these areas, and I don’t think having one more strain in circulation adds to the general population risk.  But I’d like to see an expert’s opinion on this; interactions between Dengue strains are important in the disease.

In any case, it reinforces (if reinforcement was necessary) the importance of proper lab procedures and security.

  1. A nice review is Morens, D., Taubenberger, J., & Fauci, A. (2009). The Persistent Legacy of the 1918 Influenza Virus New England Journal of Medicine, 361 (3), 225-229 DOI: 10.1056/NEJMp0904819[]
  2. Recent human influenza A (H1N1) viruses are closely related genetically to strains isolated in 1950.
    Nakajima K, Desselberger U, Palese P.
    Nature. 1978 Jul 27;274(5669):334-9.[][]
  3. Worobey, M. (2008). Phylogenetic Evidence against Evolutionary Stasis and Natural Abiotic Reservoirs of Influenza A Virus Journal of Virology, 82 (7), 3769-3774 DOI: 10.1128/JVI.02207-07[]
  4. I’ve previously cited
    Krasnitz, M., Levine, A., & Rabadan, R. (2008). Anomalies in the Influenza Virus Genome Database: New Biology or Laboratory Errors? Journal of Virology, 82 (17), 8947-8950 DOI: 10.1128/JVI.00101-08
    and see also

    Li, J., Dohna, H., Miller, J., Cardona, C., & Carpenter, T. (2009). Identifying errors in avian influenza virus gene sequences and implications for data usage of public databases Genomics DOI: 10.1016/j.ygeno.2009.09.005 []

  5. Cottam, E.M., Wadsworth, J., Shaw, A.E., Rowlands, R.J., Goatley, L., Maan, S., Maan, N.S., Mertens, P.P., Ebert, K., Li, Y., Ryan, E.D., Juleff, N., Ferris, N.P., Wilesmith, J.W., Haydon, D.T., King, D.P., Paton, D.J., Knowles, N.J. (2008). Transmission Pathways of Foot-and-Mouth Disease Virus in the United Kingdom in 2007. PLoS Pathogens, 4(4), e1000050. DOI: 10.1371/journal.ppat.1000050[]
  6. Apart from the fact that most of them are batshit crazy[]
  7. Aquino, V., Amarilla, A., Alfonso, H., Batista, W., & Figueiredo, L. (2009). New Genotype of Dengue Type 3 Virus Circulating in Brazil and Colombia Showed a Close Relationship to Old Asian Viruses PLoS ONE, 4 (10) DOI: 10.1371/journal.pone.0007299[][][]