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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 A Virus, H1N1 Subtype/genetics
Fulltext Hemagglutinin protein of Asian strains of human influenza virus A H1N1 binds to sialic acid--a major component of human airway receptors

Chua KH, Chai HC

Genet. Mol. Res., 2012;11(1):636-43.
PMID: 22535399 DOI: 10.4238/2012.March.16.1

Hemagglutinin (HA) protein plays an important role in binding the influenza virus to infected cells and therefore mediates infection. Deposited HA sequences of 86 Asian strains of influenza A (H1N1) viruses during the first outbreak were obtained from the NCBI database and compared. Interaction of the HA protein of influenza A (H1N1) virus with the human sialic acid receptor was also studied using bioinformatics. Overall, not more than three single-point amino acid variants/changes were observed in the HA protein region of influenza A (H1N1) virus from Asian countries when a selected group sequence comparison was made. The bioinformatics study showed that the HA protein of influenza A (H1N1) binds to the sialic acid receptor in human airway receptors, possibly key to air-borne infection in humans.

Matched MeSH terms: Influenza A Virus, H1N1 Subtype/genetics
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 A Virus, H1N1 Subtype/genetics*
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 A Virus, H1N1 Subtype/genetics*
Fulltext Epidemiological and virological characteristics of influenza viruses circulating in Cambodia from 2009 to 2011

Horm SV, Mardy S, Rith S, Ly S, Heng S, Vong S, et al.

PLoS One, 2014;9(10):e110713.
PMID: 25340711 DOI: 10.1371/journal.pone.0110713

BACKGROUND: The Cambodian National Influenza Center (NIC) monitored and characterized circulating influenza strains from 2009 to 2011.
METHODOLOGY/PRINCIPAL FINDINGS: Sentinel and study sites collected nasopharyngeal specimens for diagnostic detection, virus isolation, antigenic characterization, sequencing and antiviral susceptibility analysis from patients who fulfilled case definitions for influenza-like illness, acute lower respiratory infections and event-based surveillance. Each year in Cambodia, influenza viruses were detected mainly from June to November, during the rainy season. Antigenic analysis show that A/H1N1pdm09 isolates belonged to the A/California/7/2009-like group. Circulating A/H3N2 strains were A/Brisbane/10/2007-like in 2009 before drifting to A/Perth/16/2009-like in 2010 and 2011. The Cambodian influenza B isolates from 2009 to 2011 all belonged to the B/Victoria lineage represented by the vaccine strains B/Brisbane/60/2008 and B/Malaysia/2506/2004. Sequences of the M2 gene obtained from representative 2009-2011 A/H3N2 and A/H1N1pdm09 strains all contained the S31N mutation associated with adamantanes resistance except for one A/H1N1pdm09 strain isolated in 2011 that lacked this mutation. No reduction in the susceptibility to neuraminidase inhibitors was observed among the influenza viruses circulating from 2009 to 2011. Phylogenetic analysis revealed that A/H3N2 strains clustered each year to a distinct group while most A/H1N1pdm09 isolates belonged to the S203T clade.
CONCLUSIONS/SIGNIFICANCE: In Cambodia, from 2009 to 2011, influenza activity occurred throughout the year with peak seasonality during the rainy season from June to November. Seasonal influenza epidemics were due to multiple genetically distinct viruses, even though all of the isolates were antigenically similar to the reference vaccine strains. The drug susceptibility profile of Cambodian influenza strains revealed that neuraminidase inhibitors would be the drug of choice for influenza treatment and chemoprophylaxis in Cambodia, as adamantanes are no longer expected to be effective.

Matched MeSH terms: Influenza A Virus, H1N1 Subtype/genetics
An influenza B outbreak during the 2007/2008 winter among appropriately immunized elderly people living in a nursing home

Camilloni B, Neri M, Lepri E, Basileo M, Sigismondi N, Puzelli S, et al.

Vaccine, 2010 Nov 3;28(47):7536-41.
PMID: 20846530 DOI: 10.1016/j.vaccine.2010.08.064

The study evaluated the immunogenicity and efficacy of a trivalent subunit MF59-adjuvanted influenza vaccine (A/Wisconsin/67/05 (H3N2), A/Solomon Islands/3/06 (H1N1) and B/Malaysia/2506/04) in preventing serologically diagnosed infections in a group of 67 institutionalized elderly volunteers during 2007/2008 winter, characterized by co-circulation of drifted A/H3N2, A/H1N1 and B influenza viruses. Influenza vaccination induced a significant increase in the amounts of hemagglutination inhibiting antibodies, both against the vaccine and the epidemic drifted strains. However, vaccination did not prevent the circulation of the new drifted influenza B virus (B/Florida/4/06-like), belonging to the B/Yamagata/16/88-lineage, antigenically and genetically distinct from B/Victoria/2/87-lineage viruses from which the vaccine B strain was derived.

Matched MeSH terms: Influenza A Virus, H1N1 Subtype/genetics
Fulltext Influenza outbreaks during World Youth Day 2008 mass gathering

Blyth CC, Foo H, van Hal SJ, Hurt AC, Barr IG, McPhie K, et al.

Emerg Infect Dis, 2010 May;16(5):809-15.
PMID: 20409371 DOI: 10.3201/eid1605.091136

Influenza outbreaks during mass gatherings have been rarely described, and detailed virologic assessment is lacking. An influenza outbreak occurred during World Youth Day in Sydney, Australia, July 2008 (WYD2008). We assessed epidemiologic data and respiratory samples collected from attendees who sought treatment for influenza-like illness at emergency clinics in Sydney during this outbreak. Isolated influenza viruses were compared with seasonal influenza viruses from the 2008 influenza season. From 100 infected attendees, numerous strains were identified: oseltamivir-resistant influenza A (H1N1) viruses, oseltamivir-sensitive influenza A (H1N1) viruses, influenza A (H3N2) viruses, and strains from both influenza B lineages (B/Florida/4/2006-like and B/Malaysia/2506/2004-like). Novel viruses were introduced, and pre-WYD2008 seasonal viruses were amplified. Viruses isolated at mass gatherings can have substantial, complex, and unpredictable effects on community influenza activity. Greater flexibility by public health authorities and hospitals is required to appropriately manage and contain these outbreaks.

Matched MeSH terms: Influenza A Virus, H1N1 Subtype/genetics
Fulltext Component-specific effectiveness of trivalent influenza vaccine as monitored through a sentinel surveillance network in Canada, 2006-2007

Skowronski DM, De Serres G, Dickinson J, Petric M, Mak A, Fonseca K, et al.

J Infect Dis, 2009 Jan 15;199(2):168-79.
PMID: 19086914 DOI: 10.1086/595862

Trivalent inactivated influenza vaccine (TIV) is reformulated annually to contain representative strains of 2 influenza A subtypes (H1N1 and H3N2) and 1 B lineage (Yamagata or Victoria). We describe a sentinel surveillance approach to link influenza variant detection with component-specific vaccine effectiveness (VE) estimation.

Matched MeSH terms: Influenza A Virus, H1N1 Subtype/genetics