Polymer-bound 6' sialyl-N-acetyllactosamine protects mice infected by influenza virus.
To develop a mouse model for testing receptor attachment inhibitors of human influenza viruses, the human clinical virus isolate in MDCK cells A/NIB/23/89M (H1N1) was adapted to mice by serial passaging through mouse lungs. The adaptation enhanced the viral pathogenicity for mice, but preserved the virus receptor binding phenotype, preferential binding to 2-6-linked sialic acid receptors and low affinity for 2-3-linked receptors. Sequencing of the HA gene of the mouse-adapted virus A/NIB/23/89-MA revealed a loss of the glycosylation sites in positions 94 and 163 of HA1 and substitutions 275Asp-->Gly in HA1 and 145Asn-->Asp in HA2. The four mouse strains tested differed significantly in their sensitivity to A/NIB/23/89-MA with the sensitivity increasing in the order of BALB/cJCitMoise, C57BL/6LacSto, CBA/CaLacSto and A/SnJCitMoise strains. Testing of protective efficacy of the polyacrylamide conjugate bearing Neu5Acalpha2-6Galbeta1-4GlcNAc trisaccharide under conditions of lethal or sublethal virus infection demonstrated a strong protective effect of this preparation. In particular, aerosol treatment of mice with the polymeric attachment inhibitor on 24-110 h after infection completely prevented mortality in sensitive animals and lessened disease symptoms in more resistant mouse strains.
Gambaryan
A S
AS
M.P. Chumakov Institute of Poliomyelitis and Viral Encephalitides, Russian Academy of Medical Sciences, 142782 Moscow, Russia.
Boravleva
E Y
EY
Matrosovich
T Y
TY
Matrosovich
M N
MN
Klenk
H-D
HD
Moiseeva
E V
EV
Tuzikov
A B
AB
Chinarev
A A
AA
Pazynina
G V
GV
Bovin
N V
NV
D000606:Amino Sugars / Q000737:chemistry / Q000627:therapeutic use*; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000473:pathology / Q000517:prevention & control*; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry; D020011:Protective Agents / Q000627:therapeutic use*; D011991:Receptors, Virus / Q000378:metabolism*; D014779:Virus Replication
D000606:Amino Sugars; D000998:Antiviral Agents; D011108:Polymers; D020011:Protective Agents; D011991:Receptors, Virus; C032269:sialyl-N-acetyllactosamine