Structural requirements for the antiviral activity of the human MxA protein against Thogoto and influenza A virus.
J Biol Chem
; 289(9): 6020-7, 2014 Feb 28.
Article
en En
| MEDLINE
| ID: mdl-24448803
ABSTRACT
The interferon-induced dynamin-like MxA protein has broad antiviral activity against many viruses, including orthomyxoviruses such as influenza A and Thogoto virus and bunyaviruses such as La Crosse virus. MxA consists of an N-terminal globular GTPase domain, a connecting bundle signaling element, and the C-terminal stalk that mediates oligomerization and antiviral specificity. We previously reported that the disordered loop L4 that protrudes from the compact stalk is a key determinant of antiviral specificity against influenza A and Thogoto virus. However, the role of individual amino acids for viral target recognition remained largely undefined. By mutational analyses, we identified two regions in the C-terminal part of L4 that contribute to an antiviral interface. Mutations in the proximal motif, at positions 561 and 562, abolished antiviral activity against orthomyxoviruses but not bunyaviruses. In contrast, mutations in the distal motif, around position 577, abolished antiviral activity against both viruses. These results indicate that at least two structural elements in L4 are responsible for antiviral activity and that the proximal motif determines specificity for orthomyxoviruses, whereas the distal sequence serves a conserved structural function.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Thogotovirus
/
Gripe Humana
/
Subtipo H5N1 del Virus de la Influenza A
/
Proteínas de Resistencia a Mixovirus
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Biol Chem
Año:
2014
Tipo del documento:
Article
País de afiliación:
Alemania