Re: NIV detects three new variants of H1N1 virus
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Archive Number 20100525.1741
Published Date 25-MAY-2010
Subject PRO/AH> Influenza pandemic (H1N1) (34): Indian variants
INFLUENZA PANDEMIC (H1N1) (34): INDIAN VARIANTS
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A ProMED-mail post
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International Society for Infectious Diseases
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Date: Tue 25 May 2010
Source: The Times of India, Pune [edited]
<http://timesofindia.indiatimes.com/City-Pune/NIV-detects-3-new-variants-of-H1N1-virus-/articleshow/5970862.cms?>
The National Institute of Virology (NIV) here has detected 3 new
variants of the H1N1 virus. Fortunately, all 3 variants have shown
susceptibility to Tamiflu, the drug used in the treatment of swine
flu. However, with the virus actively acquiring new properties, NIV
scientists are apprehensive that it might develop resistance to the
medicines used in treating swine flu. "For now, there is no need to
worry. But we are closely monitoring the virus for any change in its
virulence," NIV assistant director Sarah Cherian told the Times of
India recently.
Cherian said 7 mutated variants of the virus have been found across
the world so far. "As expected of the seasonal influenza virus, the
H1N1 virus is also going through constant genetic variations which
might lead to significant changes in its antiviral resistance," she
said.
The variants of the H1N1 virus, representing both recovered and fatal
cases from major cities -- Pune, Mumbai, Delhi, Hyderabad and
Bangalore -- were analysed at the NIV, and the complete genomes of
these variants were sequenced. The results of the genetic analysis
have been published in the March 2010 issue of the US journal, PLOS
One.
The NIV study, which compared the Indian viruses with 685 whole
genomes of global viral isolates, revealed that the 1st Indian
isolate of May 2009 belonged to a subtype (clade 5) and correlated to
the time during which the dissemination of the virus was noted in
Asia.
The later isolates of the period from June to September 2009 belonged
to H1N1 variants (clades 6 and 7). The clade 7 variant was seen to be
the dominant one, though no spatio-temporal patterns were noted
within this variant, said Cherian. Among the established pathogenic
markers, no significant change was observed in the Indian variants of
the H1N1 virus.
The 1st influenza pandemic of the 21st century was declared with the
emergence of a novel influenza A (H1N1) strain in Mexico and the US
in April 2009. In its last H1N1 situation update released on 14 May
2010, the World Health Organisation said that more than 214 countries
and overseas territories or communities have reported
laboratory-confirmed cases of pandemic influenza H1N1 2009, including
over 18 036 deaths. [The most recent WHO Weekly Update (101), dated
24 May 2010 has been archived in ProMED-mail as "Influenza pandemic
(H1N1) (33): WHO update 20100522.1700." - Mod.CP]
--
Communicated by:
ProMED-mail Rapporteur Mary Marshall
[The detection of 3 genetic variants circulating in India is an
interesting observation. For the benefit of readers wishing more
precise detail, the abstract of the PLoS ONE paper is posted below.
"Title: Genetic Characterization of the Influenza A Pandemic (H1N1)
2009 Virus Isolates from India. Reference: PLoS ONE 5(3): e9693.
doi:10.1371/journal.pone.0009693
<http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0009693>.
By: Varsha A. Potdar, Mandeep S. Chadha, Santosh M. Jadhav, Jayati
Mullick, Sarah S. Cherian, Akhilesh C. Mishra At: National Institute
of Virology, Pune, India.
Abstract
Background: The influenza A pandemic H1N1 2009 (H1N1pdm) virus
appeared in India in May 2009 and thereafter, outbreaks with
considerable morbidity and mortality have been reported from many
parts of the country. Continuous monitoring of the genetic makeup of
the virus is essential to understand its evolution within the country
in relation to global diversification and to track the mutations that
may affect the behavior of the virus.
Methods: H1N1pdm viruses were isolated from both recovered and fatal
cases representing major cities and sequenced. Phylogenetic analyses
of 6 concatenated whole genomes and the hemagglutinin (HA) gene of 7
more isolates from May-September 2009 were performed with reference
to 685 whole genomes of global isolates available as of 24 Nov 2009.
Molecular characterization of all the 8 segments was carried out for
known pathogenic markers.
Results: The 1st isolate of May 2009 belonged to clade 5. Although
clade 7 was the dominant H1N1pdm lineage in India, both clades 6 and
7 were found to be co-circulating. The neuraminidase of all the
Indian isolates possessed H275, the marker for sensitivity to the
neuraminidase inhibitor oseltamivir [The H275Y mutation confers
resistance. - Mod.CP]. Some of the mutations in HA are at or in the
vicinity of antigenic sites and may, therefore, be of possible
antigenic significance. Among these, a D222G mutation in the HA
receptor binding domain was found in 2 of the 8 Indian isolates
obtained from fatal cases.
Conclusions: The majority of the 13 Indian isolates grouped in the
globally most widely circulating H1N1pdm clade 7. Further,
correlations of the mutations specific to clade 7 Indian isolates to
viral fitness and adaptability in the country remains to be
understood. The D222G mutation in HA from isolates of fatal cases
needs to be studied for pathogenicity."
The following information is relevant to these findings. In the
ProMED- mail post archived as "Influenza pandemic (H1N1) (21):
Norway, D222G mutation 20100305.0729," an analysis of Norwegian data
suggested that a correlation might exist between presence of the
D222G substitution in the HA gene and a severe clinical outcome,
reflecting an increase in pathogenicity caused by this mutation,
perhaps as a consequence of a change in cellular tropism rendering
the virus more pneumotropic. Alternatively, it is possible that the
likelihood of such mutations arising is higher in patients who fail
to fight off the virus rapidly and have virus already colonising the
lower respiratory tract.
Regarding the H275Y oseltamivir resistance mutation in the NA gene,
according to the most recent WHO update of 12 May 2010, the global
cumulative total is 289 so far. All but one of these have the H275Y
substitution and are assumed to remain sensitive to zanamivir. This
mutation was not present in the Indian isolates.
The HealthMap/ProMED-mail interactive map of India at
<http://healthmap.org/r/008o> can be used to locate the various
cities and states mentioned in this post. - Mod.CP]
