Genetic Changes in Pandemic H1N1 in Brazil Raise Concerns

Recombinomics Commentary 19:40
July 29, 2009

"The family Laguna had eight other cases of swine flu confirmed: mother, father, younger brother, three cousins, grandmother and an aunt of the girl. .

The above translation describes pandemic H1N1 infections in family members of the first confirmed H1N1 fatality in the Sao Paulo metropolitan region. The 11 year old girl, from Osasco (see map) died on June 30 and H1N1 was isolated from her blood on July 3. The HA sequence of the isolate, A/Sao Paulo/43812/2009, was released at Genbank and has three newly acquired polymorphisms. One polymorphism encodes for V252M (H3 numbering) and the nucleotide change is found in a limited number of sequences, including those from the 1918 pandemic. Other human H1N1 sequences include 2006 isolates from Peru and H1N1 isolates in circulation prior to the 1957 H2N2 pandemic. These human isolates have V252I. However, V252M is found in the 2001 swine isolate from Hong Kong, A/swine/Hong Kong/NS1659/2001 (see list here).

The second change also is non-synonymous (Q296H), and is found in multiple 2009 pandemic sequences identified worldwide (see list here), including an earlier isolate from Sao Paulo, A/Sao Paulo/2233/2009.

The third change is synonymous and also found in 2009 pandemic sequences (see list here), which are distinct from the isolates sharing the second polymorphisms. However, the synonymous polymorphism is also in the Hong Kong swine isolate providing additional evidence for acquisition via recombination.

This Sao Paulo isolate is the most recent isolate from Brazil, and may represent a change associated with the dramatic rise in fatalities in the region. Almost all of the fatalities in Brazil are in the southern region, and a high rate of fatalities has also been reported for adjacent locations in Argentina (see map). This concentration of fatal cases in southern Brazil and the Buenos Aires / Santa Fe region in Argentina and locations to the north, raise concerns that the fatalities may be linked to genetic changes in the pandemic virus circulating in the area. The present of the novel polymorphism, V252M, increases those concerns.

Recent reports from Argentina indicated there were 8 amino acid changes in recent isolates, presumably spread across all eight gene segments. The relationship of these changes to the newly acquired polymorphism in the Sao Paulo isolate would be of interest.

Release of recent sequences from isolates in Brazil, Argentina, Uraguay, and Paraguay would be useful.