Introduction
Influenza is still a major cause of health disorders and mortality worldwide and affects a large portion of the human population each year, this potential could cause epidemics in humans, such as H1N1 virus pandemic in 2009. In addition, many species of animals, including birds, pigs, horses, and dogs, can be infected with influenza viruses.12
Influenza viruses belong to the Orthomyxoviridae family defined by viruses that have a negative-sense, single-stranded, and fragmented RNA genome. There are currently 18 different hemagglutinin subtypes (H1 to H18) and 11 different neuraminidase subtypes (N1 to N11) for influenza A viruses.3 Antigenic changes occur only in the proteins of influenza virus neuraminidase and hemagglutinin, and hemagglutinin is more important than neuraminidase because hemagglutinin is more susceptible to such changes.
The history of the first influenza A (H1N1) pandemic in the 21st century (March 2009) occurred 33 years after the last pandemic of the 20th century (1976), followed by the detection of cases in the United States and many other countries. With the spread of the disease to several continents in April, the sixth phase of the pandemic was announced by the World Health Organization.4 On the other hand, the emergence and pandemic of influenza A (H1N1) virus with swine-origin occurred so suddenly that apparently the pathogenic stages in environment (first phase), pathogenicity in pigs (second phase), transmission from pig to human (third phase), limited human-to-human transmission in Mexico (fourth Phase), limited human outbreaks in the Americas (fifth Phase), and widespread epidemics across the continent (sixth Phase) occurred in less than three months.
With respect to viral epidemics that may emerge, molecular epidemiological techniques have been useful tools in detecting the source of epidemics and tracking the spread of regional or global viruses. In this regard, phylogenetic methods, a kind of mathematical modeling, provide new opportunities to study the evolutionary history of pathogens and to reconstruct the spatio-temporal and demographic dynamics of viral epidemics. Many viruses, such as the influenza virus, evolve faster than normal transmission, and phylogenetic techniques as an ideal and objective tool can be used for reconstructing spatio-temporal dynamics and transmission history.
Phylogeography is the study of historical processes that may have shaped the current geographical distribution of living species, such as viruses. Nowadays, these studies are performed according to the information obtained from the genealogy. Recent advances have made it possible to integrate the theory of coalescent into phylogeography in such a way that both demographic and spatial aspects of the epidemic are inferred simultaneously. This information is used to track the patterns of viral spread, which in turn can become effective intervention and prevention strategies and can shed light on the main factors responsible for the spread and transmission of the virus.5
One of the limitations of the traditional epidemiological approaches is their inability to estimate the path of the virus and identify the estimated time and place of virus entry into a specific geographical area based on available data. Bayesian phylogeographical approaches using nucleotide sequences have made it possible to study the path of the virus and the approximate time and place of virus entry into a population along with other characteristics such as molecular dynamics and so on. In this study, we investigate the above gaps using the Bayesian phylogeographic approach for influenza virus H1N1 serotypes in Iran and neighboring countries.