Interestingly, we found a high frequency of NA mutations A395V/T/D/S in the influenza B viruses circulating in Thailand. (accession numbers KP336040 to KP336156, KX151186 to KX151226, KX151227 to KX151324, and KX151325 to KX151393). Abstract The neuraminidase inhibitors (NAIs) oseltamivir and zanamivir are commonly used for the treatment and control of influenza A and B computer virus infection. However, the emergence of new influenza computer virus strains with reduced susceptibility to NAIs may appear with the use of these antivirals or even naturally. We therefore screened the neuraminidase (NA) sequences of seasonal influenza computer virus A(H1N1), A(H1N1)pdm09, A(H3N2), and influenza B computer virus strains identified in Thailand for the presence of substitutions previously reported to reduce susceptibility to NAIs. We initially examined oseltamivir resistance (characterized by the H275Y mutation in the NA gene) in 485 A(H1N1)pdm09 strains circulating in Thailand and found that 0.82% (4/485) had this substitution. To further evaluate the evolution of the NA gene, we also randomly selected 98 A(H1N1)pdm09, 158 A(H3N2), and 69 influenza B computer virus strains for NA gene amplification and sequencing, which revealed various amino acid mutations in the active site of the NA protein previously shown to be associated with reduced susceptibility to NAIs. Phylogenetic analysis of the influenza computer virus strains from this study and elsewhere around the world, together with the estimations of nucleotide substitution rates and selection pressure, and the predictions of B-cell epitopes and N-linked glycosylation sites all provided evidence for the ongoing evolution of NA. The overall rates of NA evolution for influenza A viruses were higher than for influenza B computer virus at the nucleotide level, although influenza B computer virus possessed more genealogical diversity than that of influenza A viruses. The continual surveillance of the antigenic changes associated with the NA protein will not only contribute to the influenza computer virus database but may also provide a better understanding of selection pressure exerted by antiviral use. Introduction The World Health Business (WHO) have highlighted that this influenza computer virus causes approximately 3 to 5 5 million cases of influenza every year, which contribute to 250,000 to 500,000 deaths and 200,000 hospitalizations annually [1]. Since 1977, the seasonal influenza A(H1N1), A(H1N1)pdm09, A(H3N2), and the influenza B computer virus have co-circulated globally [2C3]. Antivirals against influenza computer virus are effective for the prevention of these viral infections and have been shown to reduce the duration of infection, the severity of illness, and mortality [4C6]. Hemagglutinin (HA) and neuraminidase (NA) are the 10-Oxo Docetaxel two major surface glycoproteins of the influenza computer virus. HA is usually a homo-trimeric type I integral membrane protein that plays 10-Oxo Docetaxel a role in the attachment of the virion to the host receptors and is targeted by the host immune response [7C8]. NA is usually a tetrameric type II integral membrane protein with sialidase activity responsible for releasing the newly produced viral particles [8C9]. Current treatment for influenza computer virus infection is limited to a single class of antivirals, namely neuraminidase inhibitors (NAIs) [10C11]. Although the structure of the catalytic and antigenic sites of NA protein of the influenza computer virus was identified in 1983 [12], the continual evolution of the NA gene has resulted from nucleotide substitutions, insertions, 10-Oxo Docetaxel and deletions [13]. The relatively low fidelity of the influenza computer virus RNA polymerase contributes to the high rate of replication errors, which occur at approximately 1 in 104 bases per replication cycle [14]. Thus, each round of replication leads to a populace with more variants [13]. The resulting changes in the NA protein can change the computer virus so that it can escape the hosts immune system or be resistant to antiviral drugs and persist in the human population [10, 15]. Currently, clinically approved NAIs include oseltamivir, zanamivir, peramivir, and laninamivir [16C17]. However, reports of emerging resistance to NAIs among some circulating strains of influenza computer virus have appeared [18C24]. Therefore, careful surveillance of the genetic variability of the NA gene may provide important insight into the evolution of the influenza computer virus. In this study, we examined for the presence of NA substitutions associated with reduced susceptibility to NAIs among influenza A and B viruses identified in Thailand. We further identified the B-cell epitopes and the potential N-linked glycosylation sites of the NA proteins, and to determine the evolutionary dynamics of the NA genes of strains of.In addition, we screened for the presence of NA molecular markers associated with reduced NAIs susceptibility. The seasonal A(H1N1) viruses circulating in Thailand from 2004 to 2006 were oseltamivir-susceptible and belonged to clades 1, 2A, and 2C (Fig 1). to KX151393). Abstract The neuraminidase inhibitors (NAIs) oseltamivir and zanamivir are commonly used for the treatment and control of influenza A and B computer virus infection. However, the emergence of new influenza computer virus strains with reduced susceptibility to NAIs may appear with the use of these antivirals or even naturally. We therefore screened the neuraminidase (NA) sequences of seasonal influenza computer virus A(H1N1), A(H1N1)pdm09, A(H3N2), and influenza B computer virus strains identified in Thailand for the presence of substitutions previously reported to reduce susceptibility to NAIs. We initially examined oseltamivir resistance (characterized by the H275Y mutation in the NA gene) in 485 A(H1N1)pdm09 strains circulating in Thailand and found that 0.82% (4/485) had this substitution. To further evaluate the evolution of the NA gene, we also randomly selected 98 A(H1N1)pdm09, 158 A(H3N2), and 69 influenza B computer virus strains for NA gene amplification and sequencing, which revealed various amino acid Nrp1 mutations in the active site of the NA protein previously shown to be associated with reduced susceptibility to NAIs. Phylogenetic analysis of the influenza computer virus strains from this study and elsewhere around the world, together with the estimations of nucleotide substitution rates and selection pressure, and the predictions of B-cell epitopes and N-linked glycosylation sites all provided evidence for the ongoing evolution of NA. The overall rates of NA evolution for influenza A viruses were higher than for influenza B computer virus at the nucleotide level, although influenza B computer virus possessed more genealogical diversity than that of influenza A viruses. The continual surveillance of the antigenic changes associated with the NA protein will not only contribute to the influenza computer virus database but may also provide a better understanding of selection pressure exerted by antiviral use. Introduction The World Health Business (WHO) have highlighted that this influenza computer virus causes approximately 3 to 5 5 million cases of influenza every year, which donate to 250,000 to 500,000 fatalities and 200,000 hospitalizations yearly [1]. Since 1977, the seasonal influenza A(H1N1), A(H1N1)pdm09, A(H3N2), as well as the influenza B disease have co-circulated internationally [2C3]. Antivirals against influenza disease work for preventing these viral attacks and have been proven to lessen the length of infection, the severe nature of disease, and mortality [4C6]. Hemagglutinin (HA) and neuraminidase (NA) will be the two main surface glycoproteins from the influenza disease. HA can be a homo-trimeric type I essential membrane proteins that is important in the connection from the virion towards the sponsor receptors and it is targeted from the sponsor immune system response [7C8]. NA can be a tetrameric type II essential membrane proteins with sialidase activity in charge of releasing the recently produced viral contaminants [8C9]. Current treatment for influenza disease infection is bound to an individual course of antivirals, specifically neuraminidase inhibitors (NAIs) [10C11]. Even though the structure from the catalytic and antigenic sites of NA proteins from the influenza disease was determined in 1983 [12], the continual advancement from the NA gene offers resulted from nucleotide substitutions, insertions, and deletions [13]. The fairly low fidelity 10-Oxo Docetaxel from the influenza disease RNA polymerase plays a part in the higher rate of replication mistakes, which happen at around 1 in 104 bases per replication routine [14]. Therefore, each circular of replication qualified prospects to a human population with more variations [13]. The ensuing adjustments in the NA proteins can alter the disease such that it can get away the hosts disease fighting capability or become resistant to antiviral medicines and persist in the population [10, 15]. Presently, clinically authorized NAIs consist of oseltamivir, zanamivir, peramivir, and laninamivir [16C17]. Nevertheless, reports of growing level of resistance to NAIs among some circulating strains of influenza disease have made an appearance [18C24]. Therefore, cautious surveillance from the hereditary variability from the NA gene might.