Linked Life Data

1448912

Source:http://linkedlifedata.com/resource/pubmed/id/1448912

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1992-12-30
pubmed:abstractText
Mutations in the influenza M2 membrane protein which confer resistance to the antiviral drug amantadine are exclusively located within the transmembrane region of the molecule. The influence of specific amino acid substitutions on the activity of the M2 protein in influenza A virus-infected cells is assessed in this report by their effects upon haemagglutinin (HA) stability and virus growth. A number of amino acid substitutions, e.g., L26H, A30T, S31N and G34E reduced the activity of the M2 protein of A/chicken/Germany/34 (Rostock) and caused a substantial increase in expression of the low-pH form of HA. The adverse effects of the mutations on virus replication were evident from changes selected during subsequent passage of the mutant viruses in the presence or absence of amantadine: reversion to wt, the acquisition of a second suppressor mutation in M2, or the appearance of a complementary mutation in HA which increased its pH stability. In contrast, 127T and 127S, mutations which were most readily selected following passage of the wt virus in the presence of drug, caused an increase in M2 activity. Furthermore, in double mutants the 127T mutation suppressed the attenuating effects of the A30T and S31N mutations on M2 activity. The influence of primary structure on the consequences of particular amino acid changes was further emphasized by the contrasting effects of the G34E mutation on the activities of two closely related proteins, causing an increase in the activity of the M2 of A/chicken/Germany/27 (Weybridge) as opposed to the decrease in activity of the Rostock protein. Estimates of differences in trans Golgi pH based on the degree of conversion of HA to the low-pH form, or complementation of differences in pH stability of mutant HAs, indicate that changes in M2 may influence pH within the transport pathway by as much as 0.6. The results thus provide further evidence that M2 regulates transmembrane pH gradients in the trans Golgi. Incompatibility between particular HA and M2 components and the selection of M2 mutants with suboptimal activity stresses the essential relationship between the structures and functions of these two virus proteins.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0042-6822
pubmed:author
pubmed:issnType
Print
pubmed:volume
191
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
541-9
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Influence of amantadine resistance mutations on the pH regulatory function of the M2 protein of influenza A viruses.
pubmed:affiliation
National Institute for Medical Research, Mill Hill, London, U.K.
pubmed:publicationType
Journal Article