Displaying publications 21 - 40 of 52 in total

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  1. A case-control study of influenza vaccine effectiveness among Malaysian pilgrims attending the Haj in Saudi Arabia
    Mustafa AN, Gessner BD, Ismail R, Yusoff AF, Abdullah N, Ishak I, et al.
    Int J Infect Dis, 2003 Sep;7(3):210-4.
    PMID: 14563225
    To determine influenza vaccine effectiveness against clinically defined influenza-like illness among Malaysian pilgrims attending the Haj in Saudi Arabia.
    Matched MeSH terms: Influenza, Human/virology
  2. Expression of surface-bound nonstructural 1 (NS1) protein of influenza virus A H5N1 on Lactobacillus casei strain C1
    Tan TS, Syed Hassan S, Yap WB
    Lett Appl Microbiol, 2017 Jun;64(6):446-451.
    PMID: 28370088 DOI: 10.1111/lam.12738
    The study aimed to construct a recombinant Lactobacillus casei expressing the nonstructural (NS) 1 protein of influenza A virus H5N1 on its cell wall. The NS1 gene was first amplified and fused to the pSGANC332 expression plasmid. The NS1 protein expression was carried out by Lact. casei strain C1. PCR screening and DNA sequencing confirmed the presence of recombinant pSG-NS1-ANC332 plasmid in Lact. casei. The plasmid was stably maintained (98·94 ± 1·65%) by the bacterium within the first 20 generations without selective pressure. The NS1 was expressed as a 49-kDa protein in association with the anchoring peptide. The yield was 1·325 ± 0·065 μg mg(-1) of bacterial cells. Lactobacillus casei expressing the NS1 on its cell wall was red-fluorescently stained, but the staining was not observed on Lact. casei carrying the empty pSGANC332. The results implied that Lact. casei strain C1 is a promising host for the expression of surface-bound NS1 protein using the pSGANC332 expression plasmid.

    SIGNIFICANCE AND IMPACT OF THE STUDY: The study has demonstrated, for the first time, the expression of nonstructural 1 (NS1) protein of influenza A virus H5N1 on the cell wall of Lactobacillus casei using the pSGANC332 expression plasmid. Display of NS1 protein on the bacterial cell wall was evident under an immunofluorescence microscopic observation. Lactobacillus casei carrying the NS1 protein could be developed into a universal oral influenza vaccine since the NS1 is highly conserved among influenza viruses.

    Matched MeSH terms: Influenza, Human/virology
  3. Antiviral activity of Embelia ribes Burm. f. against influenza virus in vitro
    Hossan MS, Fatima A, Rahmatullah M, Khoo TJ, Nissapatorn V, Galochkina AV, et al.
    Arch Virol, 2018 Aug;163(8):2121-2131.
    PMID: 29633078 DOI: 10.1007/s00705-018-3842-6
    Viral respiratory infections are raising serious concern globally. Asian medicinal plants could be useful in improving the current treatment strategies for influenza. The present study examines the activity of five plants from Bangladesh against influenza virus. MDCK cells infected with influenza virus A/Puerto Rico/8/34 (H1N1) were treated with increasing concentrations of ethyl acetate extracts, and their cytotoxicity (CC50), virus-inhibiting activity (IC50), and selectivity index (SI) were calculated. The ethyl acetate extract of fruits of Embelia ribes Burm. f. (Myrsinaceae) had the highest antiviral activity, with an IC50 of 0.2 µg/mL and a SI of 32. Its major constituent, embelin, was further isolated and tested against the same virus. Embelin demonstrated antiviral activity, with an IC50 of 0.3 µM and an SI of 10. Time-of-addition experiments revealed that embelin was most effective when added at early stages of the viral life cycle (0-1 h postinfection). Embelin was further evaluated against a panel of influenza viruses including influenza A and B viruses that were susceptible or resistant to rimantadine and oseltamivir. Among the viruses tested, avian influenza virus A/mallard/Pennsylvania/10218/84 (H5N2) was the most susceptible to embelin (SI = 31), while A/Aichi/2/68 (H3N2) virus was the most resistant (SI = 5). In silico molecular docking showed that the binding site for embelin is located in the receptor-binding domain of the viral hemagglutinin. The results of this study provide evidence that E. ribes can be used for development of a novel alternative anti-influenza plant-based agent.
    Matched MeSH terms: Influenza, Human/virology*
  4. The influenza A virus matrix protein 2 undergoes retrograde transport from the endoplasmic reticulum into the cytoplasm and bypasses cytoplasmic proteasomal degradation
    Bhowmick S, Chakravarty C, Sellathamby S, Lal SK
    Arch Virol, 2017 Apr;162(4):919-929.
    PMID: 27942972 DOI: 10.1007/s00705-016-3153-8
    The matrix protein 2 (M2) is a spliced product of segment 7 genome of influenza A virus. Previous studies indicate its role in uncoating of the viral ribonucleoprotein complex during viral entry and in membrane scission while budding. Despite its crucial role in the viral life cycle, little is known about its subcellular distribution and dynamics. In this study, we have shown that the M2 protein is translocated from the membrane to the cytoplasm by a retrograde route via endosomes and the Golgi network. It utilizes retromer cargo while moving from the endosome to the trans-Golgi network and prevents endosome fusion with the lysosome. Further, M2 interacts with the endoplasmic-reticulum-resident AAA-ATPase p97 for its release into the cytoplasm. Our study also revealed that the M2 protein in the cellular milieu does not undergo ubiquitin-mediated proteasomal degradation. The migration of M2 through this pathway inside the infected cell suggests possible new roles that the M2 protein may have in the host cytoplasm, apart from its previously described functions.
    Matched MeSH terms: Influenza, Human/virology*
  5. Intercontinental circulation of human influenza A(H1N2) reassortant viruses during the 2001-2002 influenza season
    Xu X, Smith CB, Mungall BA, Lindstrom SE, Hall HE, Subbarao K, et al.
    J Infect Dis, 2002 Nov 15;186(10):1490-3.
    PMID: 12404167
    Reassortant influenza A viruses bearing the H1 subtype of hemagglutinin (HA) and the N2 subtype of neuraminidase (NA) were isolated from humans in the United States, Canada, Singapore, Malaysia, India, Oman, Egypt, and several countries in Europe during the 2001-2002 influenza season. The HAs of these H1N2 viruses were similar to that of the A/New Caledonia/20/99(H1N1) vaccine strain both antigenically and genetically, and the NAs were antigenically and genetically related to those of recent human H3N2 reference strains, such as A/Moscow/10/99(H3N2). All 6 internal genes of the H1N2 reassortants examined originated from an H3N2 virus. This article documents the first widespread circulation of H1N2 reassortants on 4 continents. The current influenza vaccine is expected to provide good protection against H1N2 viruses, because it contains the A/New Caledonia/20/99(H1N1) and A/Moscow/10/99(H3N2)-like viruses, which have H1 and N2 antigens that are similar to those of recent H1N2 viruses.
    Matched MeSH terms: Influenza, Human/virology*
  6. Influenza A virus neuraminidase protein interacts with Hsp90, to stabilize itself and enhance cell survival
    Kumar P, Gaur P, Kumari R, Lal SK
    J Cell Biochem, 2019 04;120(4):6449-6458.
    PMID: 30335904 DOI: 10.1002/jcb.27935
    Neuraminidase protein (NA) of influenza A virus (IAV) is popularly known for its sialidase function to assist in the release of progeny virus. However, involvement of NA in other stages of the IAV life cycle also indicates its multifunctional nature and necessity to interact with other host proteins. Here, we report a host protein-heat shock protein 90 (Hsp90), as a novel interacting partner of IAV NA. A classical yeast two-hybrid screen was conducted to identify a new host interacting partner for NA and the interaction was further validated by coimmunoprecipitation from cells, transiently expressing both proteins and also from IAV-infected cells. Confocal imaging showed that both proteins colocalized in the cytoplasm in transfected host cells. Interestingly, increased levels of NA in the presence of Hsp90 was observed, which tends to decrease if adenosine triphosphatase activity of Hsp90 is inhibited using 17-N-allylamino-17-demethoxygeldanamycin (17AAG). This establishes viral NA as a client protein of host chaperone Hsp90 contributing toward NA's stability via the NA-Hsp90 interaction. This is the first report showing the interaction of NA with Hsp90 and its role in stabilizing viral NA thus preventing it from degradation. Enhanced cell survival in the presence of this interaction was also observed, thus suggesting the requirement of stable viral NA, post-IAV infection, for efficient virus production in infected mammalian cells.
    Matched MeSH terms: Influenza, Human/virology*
  7. Fulltext Nanoparticles in influenza subunit vaccine development: Immunogenicity enhancement
    Khalaj-Hedayati A, Chua CLL, Smooker P, Lee KW
    Influenza Other Respir Viruses, 2020 Jan;14(1):92-101.
    PMID: 31774251 DOI: 10.1111/irv.12697
    The threat of novel influenza infections has sparked research efforts to develop subunit vaccines that can induce a more broadly protective immunity by targeting selected regions of the virus. In general, subunit vaccines are safer but may be less immunogenic than whole cell inactivated or live attenuated vaccines. Hence, novel adjuvants that boost immunogenicity are increasingly needed as we move toward the era of modern vaccines. In addition, targeting, delivery, and display of the selected antigens on the surface of professional antigen-presenting cells are also important in vaccine design and development. The use of nanosized particles can be one of the strategies to enhance immunogenicity as they can be efficiently recognized by antigen-presenting cells. They can act as both immunopotentiators and delivery system for the selected antigens. This review will discuss on the applications, advantages, limitations, and types of nanoparticles (NPs) used in the preparation of influenza subunit vaccine candidates to enhance humoral and cellular immune responses.
    Matched MeSH terms: Influenza, Human/virology
  8. A previously unknown reovirus of bat origin is associated with an acute respiratory disease in humans
    Chua KB, Crameri G, Hyatt A, Yu M, Tompang MR, Rosli J, et al.
    Proc Natl Acad Sci U S A, 2007 Jul 03;104(27):11424-9.
    PMID: 17592121
    Respiratory infections constitute the most widespread human infectious disease, and a substantial proportion of them are caused by unknown etiological agents. Reoviruses (respiratory enteric orphan viruses) were first isolated from humans in the early 1950s and so named because they were not associated with any known disease. Here, we report a previously unknown reovirus (named "Melaka virus") isolated from a 39-year-old male patient in Melaka, Malaysia, who was suffering from high fever and acute respiratory disease at the time of virus isolation. Two of his family members developed similar symptoms approximately 1 week later and had serological evidence of infection with the same virus. Epidemiological tracing revealed that the family was exposed to a bat in the house approximately 1 week before the onset of the father's clinical symptoms. Genome sequence analysis indicated a close genetic relationship between Melaka virus and Pulau virus, a reovirus isolated in 1999 from fruit bats in Tioman Island, Malaysia. Screening of sera collected from human volunteers on the island revealed that 14 of 109 (13%) were positive for both Pulau and Melaka viruses. This is the first report of an orthoreovirus in association with acute human respiratory diseases. Melaka virus is serologically not related to the different types of mammalian reoviruses that were known to infect humans asymptomatically. These data indicate that bat-borne reoviruses can be transmitted to and cause clinical diseases in humans.
    Matched MeSH terms: Influenza, Human/virology
  9. Isolation of an influenza C virus introduced into Japan by a traveler from Malaysia
    Matsuzaki Y, Sato K, Sugawara K, Takashita E, Muraki Y, Morishita T, et al.
    J Clin Microbiol, 2005 Feb;43(2):993-5.
    PMID: 15695727
    An influenza C virus was isolated from a Japanese traveler who had visited Malaysia in April 1999. Phylogenetic analysis indicated that the genome composition of this virus was distinct from that of any other strain isolated in Japan. The possibility that a genetically unique influenza C virus was introduced into Japan by a traveler is shown.
    Matched MeSH terms: Influenza, Human/virology*
  10. Fulltext Epidemiology and seasonality of respiratory viral infections in hospitalized children in Kuala Lumpur, Malaysia: a retrospective study of 27 years
    Khor CS, Sam IC, Hooi PS, Quek KF, Chan YF
    BMC Pediatr, 2012;12:32.
    PMID: 22429933 DOI: 10.1186/1471-2431-12-32
    Viral respiratory tract infections (RTI) are relatively understudied in Southeast Asian tropical countries. In temperate countries, seasonal activity of respiratory viruses has been reported, particularly in association with temperature, while inconsistent correlation of respiratory viral activity with humidity and rain is found in tropical countries. A retrospective study was performed from 1982-2008 to investigate the viral etiology of children (≤ 5 years old) admitted with RTI in a tertiary hospital in Kuala Lumpur, Malaysia.
    Matched MeSH terms: Influenza, Human/virology
  11. Fulltext Investigation of a potential zoonotic transmission of orthoreovirus associated with acute influenza-like illness in an adult patient
    Chua KB, Voon K, Yu M, Keniscope C, Abdul Rasid K, Wang LF
    PLoS One, 2011;6(10):e25434.
    PMID: 22022394 DOI: 10.1371/journal.pone.0025434
    Bats are increasingly being recognized as important reservoir hosts for a large number of viruses, some of them can be highly virulent when they infect human and livestock animals. Among the new bat zoonotic viruses discovered in recent years, several reoviruses (respiratory enteric orphan viruses) were found to be able to cause acute respiratory infections in humans, which included Melaka and Kampar viruses discovered in Malaysia, all of them belong to the genus Orthoreovirus, family Reoviridae. In this report, we describe the isolation of a highly related virus from an adult patient who suffered acute respiratory illness in Malaysia. Although there was no direct evidence of bat origin, epidemiological study indicated the potential exposure of the patient to bats before the onset of disease. The current study further demonstrates that spillover events of different strains of related orthoreoviruses from bats to humans are occurring on a regular basis, which calls for more intensive and systematic surveillances to fully assess the true public health impact of these newly discovered bat-borne zoonotic reoviruses.
    Matched MeSH terms: Influenza, Human/virology*
  12. Fulltext Molecular analysis of 2009 pandemic influenza A(H1N1) in Malaysia associated with mild and severe infections
    Balraj P, Sidek H, Suppiah J, Khoo AS, Saat Z
    Malays J Pathol, 2011 Jun;33(1):7-12.
    PMID: 21874745 MyJurnal
    The 2009 pandemic influenza A(H1N1) was first detected in Malaysia in May 2009. It quickly spread in the general population and contributed to a number of influenza-like illness. The objective of the study is to characterize genetic changes in early Malaysian isolates of mild and severe illness of the novel influenza, and to compare sequences of viruses circulating in Malaysia to those in other countries between May to September 2009. Viral isolates of 56 mild cases and 10 severe (intensive care unit or fatal) cases were sequenced for haemagglutinin (HA) and neuraminidase (NA). Genome sequencing of the viral RNA was conducted on 5 isolates (3 were from fatal cases). Highly conserved sequences with few sporadic variations were identified in HA and NA. E374K and D222N were identified in 2 viral isolates from patients with severe illness. Phylogenetic analysis showed close genetic relatedness to the vaccine strain A/California/07/09 and other isolates circulating worldwide during the same period. Sporadic variations were identified in the viral isolates, however a larger sample size is required to make associations with disease severity.
    Matched MeSH terms: Influenza, Human/virology
  13. Fulltext Monitoring of the h275y mutation in pandemic influenza A(H1N1) 2009 strains isolated in Malaysia
    Suppiah J, Yusof MA, Othman KA, Saraswathy TS, Thayan R, Kasim FM, et al.
    Southeast Asian J. Trop. Med. Public Health, 2011 Jan;42(1):100-4.
    PMID: 21323171
    The 2009 pandemic influenza A(H1N1) infection in Malaysia was first reported in May 2009 and oseltamivir was advocated for confirmed cases in postexposure prophylaxis. However, there are cases of oseltamivir-resistance reported among H1N1-positive patients in other countries. Resistance is due to substitution of histidine by tyrosine at residue 275 (H275Y) of neuraminidase (NA). In this study, we have employed Sanger sequencing method to investigate the occurrence of mutations in NA segments of 67 pandemic 2009 A(H1N1) viral isolates from Malaysian patients that could lead to probable oseltamivir resistance. The sequencing analysis did not yield mutation at residue 275 for all 67 isolates indicating that our viral isolates belong to the wild type and do not confer resistance to oseltamivir.
    Matched MeSH terms: Influenza, Human/virology*
  14. Molecular characterization of influenza viruses circulating in Northern Italy during two seasons (2005/2006 and 2006/2007) of low influenza activity
    Pariani E, Amendola A, Zappa A, Bianchi S, Colzani D, Anselmi G, et al.
    J Med Virol, 2008 Nov;80(11):1984-91.
    PMID: 18814246 DOI: 10.1002/jmv.21323
    The influenza activity and circulation of influenza viruses in Lombardy (the most populous Italian region) were observed during two consecutive seasons (2005/2006 and 2006/2007) characterized by low influenza activity by the Italian Influenza Surveillance Network. The molecular characteristics of circulating viruses were analyzed to evaluate the introduction of new variants and emergence of vaccine-escape viruses. In both seasons, the epidemic in Lombardy was sustained almost exclusively by influenza A viruses, accounting for 80.5% and 93.6% of total detections, respectively, and the co-circulation of A/H3 viruses belonging to distinct phylogenetic groups was observed. The A/H1N1 viruses isolated during the 2005/2006 season were closely related to A/New Caledonia/20/99, while the hemagglutinin (HA) sequences of the A/H1N1 viruses from the 2006/2007 season exhibited a greater diversity. These viruses were A/Solomon Islands/3/2006-like and showed several variants. All B isolates were similar to B/Malaysia/2506/2004 belonging to the B/Victoria/2/87-lineage. Influenza B virus was the dominant virus in Europe in the 2005/2006 season and accounted for the 20% of total detections in Lombardy. Overall, the viruses studied presented heterogeneity in their HA sequences suggesting the circulation of a miscellaneous set of variants during the two seasons notwithstanding the medium-low activity of influenza. The importance of virological surveillance of influenza viruses is recognized widely and the molecular characterization of the viruses, especially in vaccinated subjects, is of particular importance to evaluate the introduction and circulation of new variants.
    Matched MeSH terms: Influenza, Human/virology*
  15. [The 2005-2006 influenza season in the Netherlands and the vaccine composition for the 2006-2007 season]
    Rimmelzwaan GF, de Jong JC, Donker GA, Meijer A, Fouchier RA, Osterhaus AD
    Ned Tijdschr Geneeskd, 2006 Oct 7;150(40):2209-14.
    PMID: 17061434
    The first sign of influenza activity in the Netherlands during the 2005-2006 influenza season was the isolation of influenza viruses in the last week of 2005. From Week 1 of 2006 onwards, an increase in clinical influenza activity was also observed that did not return to baseline levels until Week 15. Two waves of influenza activity were observed with peak incidences of 13.8 and 9.8 influenza-like illnesses per 10,000 inhabitants on Weeks 7 and 12, respectively. The first wave of influenza was caused primarily by influenza B viruses, whereas the second wave was caused predominantly by influenza A/H3N2 viruses. The influenza B viruses appeared to belong to two different phylogenetic lineages and were antigenically distinguishable from the vaccine strain. The isolated influenza A/H3N2 viruses were closely related to the vaccine strain for this subtype and only minor antigenic differences with the vaccine strain were observed for a limited number of isolates. Only a small number of influenza A/H1N1 viruses were isolated, which all closely resembled the H1N1 vaccine strain. For the 2006-2007 influenza season, the World Health Organization has recommended the following vaccine composition: A/Wisconsin/67/05 (H3N2), A/New Caledonia/20/99 (H1N1) and B/Malaysia/2506/05.
    Matched MeSH terms: Influenza, Human/virology
  16. Molecular analysis of isolates from influenza B outbreaks in the U.S. and Nepal, 2005
    Daum LT, Canas LC, Klimov AI, Shaw MW, Gibbons RV, Shrestha SK, et al.
    Arch Virol, 2006 Sep;151(9):1863-74.
    PMID: 16736092
    Currently circulating influenza B viruses can be divided into two antigenically and genetically distinct lineages referred to by their respective prototype strains, B/Yamagata/16/88 and B/Victoria/2/87, based on amino acid differences in the hemagglutinin surface glycoprotein. During May and July 2005, clinical specimens from two early season influenza B outbreaks in Arizona and southeastern Nepal were subjected to antigenic (hemagglutinin inhibition) and nucleotide sequence analysis of hemagglutinin (HA1), neuraminidase (NA), and NB genes. All isolates exhibited little reactivity with the B/Shanghai/361/2002 (B/Yamagata-like) vaccine strain and significantly reduced reactivity with the previous 2003/04 B/Hong Kong/330/2001 (B/Victoria-like) vaccine strain. The majority of isolates were antigenically similar to B/Hawaii/33/2004, a B/Victoria-like reference strain. Sequence analysis indicated that 33 of 34 isolates contained B/Victoria-like HA and B/Yamagata-like NA and NB proteins. Thus, these outbreak isolates are both antigenically and genetically distinct from the current Northern Hemisphere vaccine virus strain as well as the previous 2003-04 B/Hong Kong/330/2001 (B/Victoria lineage) vaccine virus strain but are genetically similar to B/Malaysia/2506/2004, the vaccine strain proposed for the coming seasons in the Northern and Southern Hemispheres. Since these influenza B outbreaks occurred in two very distant geographical locations, these viruses may continue to circulate during the 2006 season, underscoring the importance of rapid molecular monitoring of HA, NA and NB for drift and reassortment.
    Matched MeSH terms: Influenza, Human/virology*
  17. Susceptibility of highly pathogenic A(H5N1) avian influenza viruses to the neuraminidase inhibitors and adamantanes
    Hurt AC, Selleck P, Komadina N, Shaw R, Brown L, Barr IG
    Antiviral Res, 2007 Mar;73(3):228-31.
    PMID: 17112602
    Since 2003, highly pathogenic A(H5N1) influenza viruses have been the cause of large-scale death in poultry and the subsequent infection and death of over 140 humans. A group of 55 influenza A(H5N1) viruses isolated from various regions of South East Asia between 2004 and 2006 were tested for their susceptibility to the anti-influenza drugs the neuraminidase inhibitors and adamantanes. The majority of strains were found to be fully sensitive to the neuraminidase inhibitors oseltamivir carboxylate, zanamivir and peramivir; however two strains demonstrated increased IC50 values. Sequence analysis of these strains revealed mutations in the normally highly conserved residues 116 and 117 of the N1 neuraminidase. Sequence analysis of the M2 gene showed that all of the A(H5N1) viruses from Vietnam, Malaysia and Cambodia contained mutations (L26I and S31N) associated with resistance to the adamantane drugs (rimantadine and amantadine), while strains from Indonesia were found to be a mix of both adamantane resistant (S31N) and sensitive viruses. None of the A(H5N1) viruses from Myanmar contained mutations known to confer adamantane resistance. These results support the use of neuraminidase inhibitors as the most appropriate class of antiviral drug to prevent or treat human A(H5N1) virus infections.
    Matched MeSH terms: Influenza, Human/virology*
  18. Fulltext Using routine surveillance data to estimate the epidemic potential of emerging zoonoses: application to the emergence of US swine origin influenza A H3N2v virus
    Cauchemez S, Epperson S, Biggerstaff M, Swerdlow D, Finelli L, Ferguson NM
    PLoS Med, 2013;10(3):e1001399.
    PMID: 23472057 DOI: 10.1371/journal.pmed.1001399
    BACKGROUND: Prior to emergence in human populations, zoonoses such as SARS cause occasional infections in human populations exposed to reservoir species. The risk of widespread epidemics in humans can be assessed by monitoring the reproduction number R (average number of persons infected by a human case). However, until now, estimating R required detailed outbreak investigations of human clusters, for which resources and expertise are not always available. Additionally, existing methods do not correct for important selection and under-ascertainment biases. Here, we present simple estimation methods that overcome many of these limitations.

    METHODS AND FINDINGS: Our approach is based on a parsimonious mathematical model of disease transmission and only requires data collected through routine surveillance and standard case investigations. We apply it to assess the transmissibility of swine-origin influenza A H3N2v-M virus in the US, Nipah virus in Malaysia and Bangladesh, and also present a non-zoonotic example (cholera in the Dominican Republic). Estimation is based on two simple summary statistics, the proportion infected by the natural reservoir among detected cases (G) and among the subset of the first detected cases in each cluster (F). If detection of a case does not affect detection of other cases from the same cluster, we find that R can be estimated by 1-G; otherwise R can be estimated by 1-F when the case detection rate is low. In more general cases, bounds on R can still be derived.

    CONCLUSIONS: We have developed a simple approach with limited data requirements that enables robust assessment of the risks posed by emerging zoonoses. We illustrate this by deriving transmissibility estimates for the H3N2v-M virus, an important step in evaluating the possible pandemic threat posed by this virus. Please see later in the article for the Editors' Summary.

    Matched MeSH terms: Influenza, Human/virology*
  19. Fulltext Upregulation of miR-101 during Influenza A Virus Infection Abrogates Viral Life Cycle by Targeting mTOR Pathway
    Sharma S, Chatterjee A, Kumar P, Lal S, Kondabagil K
    Viruses, 2020 04 15;12(4).
    PMID: 32326380 DOI: 10.3390/v12040444
    Micro RNAs (miRNAs) are a class of small non-coding single-stranded RNA, which play an important role in modulating host-Influenza A virus (IAV) crosstalk. The interplay between influenza and miRNA interaction is defined by a plethora of complex mechanisms, which are not fully understood yet. Here, we demonstrate that in IAV infected A549 cells, a synchronous increase was observed in the expression of mTOR up to 24 hpi and significant downregulation at 48 hpi. Additionally, NP of IAV interacts with mTOR and modulates the levels of mTOR mRNA and protein, thus regulating the translation of host cell. RNA sequencing and qPCR analysis of IAV-infected A549 cells and NP transfected cells revealed that miR-101 downregulates mTOR transcripts at later stages of infection. Ectopic expression of miR-101 mimic led to a decrease in expression of NP, a reduction in IAV titer and replication. Moreover, treatment of the cells with Everolimus, a potent inhibitor of mTOR, resulted in an increase of miR-101 transcript levels, which further suppressed the viral protein synthesis. Collectively, the data suggest a novel mechanism that IAV stimulates mTOR pathway at early stages of infection; however, at a later time-point, positive regulation of miR-101 restrains the mTOR expression, and hence, the viral propagation.
    Matched MeSH terms: Influenza, Human/virology*
  20. Influenza in the Asia-Pacific region: Findings and recommendations from the Global Influenza Initiative
    Cowling BJ, Caini S, Chotpitayasunondh T, Djauzi S, Gatchalian SR, Huang QS, et al.
    Vaccine, 2017 Feb 07;35(6):856-864.
    PMID: 28081970 DOI: 10.1016/j.vaccine.2016.12.064
    The fourth roundtable meeting of the Global Influenza Initiative (GII) was held in Hong Kong, China, in July 2015. An objective of this meeting was to gain a broader understanding of the epidemiology, surveillance, vaccination policies and programs, and obstacles to vaccination of influenza in the Asia-Pacific region through presentations of data from Australia, Hong Kong, India, Indonesia, Malaysia, New Zealand, the Philippines, Taiwan, Thailand, and Vietnam. As well as a need for improved levels of surveillance in some areas, a range of factors were identified that act as barriers to vaccination in some countries, including differences in climate and geography, logistical challenges, funding, lack of vaccine awareness and education, safety concerns, perceived lack of vaccine effectiveness, and lack of inclusion in national guidelines. From the presentations at the meeting, the GII discussed a number of recommendations for easing the burden of influenza and overcoming the current challenges in the Asia-Pacific region. These recommendations encompass the need to improve surveillance and availability of epidemiological data; the development and publication of national guidelines, where not currently available and/or that are in line with those proposed by the World Health Organization; the requirement for optimal timing of vaccination programs according to local or country-specific epidemiology; and calls for advocacy and government support of vaccination programs in order to improve availability and uptake and coverage. In conclusion, in addition to the varied epidemiology of seasonal influenza across this diverse region, there are a number of logistical and resourcing issues that present a challenge to the development of optimally effective vaccination strategies and that need to be overcome to improve access to and uptake of seasonal influenza vaccines. The GII has developed a number of recommendations to address these challenges and improve the control of influenza.
    Matched MeSH terms: Influenza, Human/virology
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