tetano
Editor, Senior Moderator
Poult Sci
. 2026 May 25;105(9):107178.
doi: 10.1016/j.psj.2026.107178. Online ahead of print.
Strain-specific responses of avian influenza virus to disruption of solute carrier family 35 member A1 (SLC35A1) in chicken cells
Heidi Liu[SUP] 1 [/SUP], Jéssica Moraes Cruvinel[SUP] 2 [/SUP], Wesley C Warren[SUP] 2 [/SUP], Wenjun Ma[SUP] 3 [/SUP], Paula R Chen[SUP] 4 [/SUP]
Affiliations
Avian influenza virus (AIV) poses a persistent threat to poultry health and food security, with conventional control measures offering limited protection. A promising alternative is the use of gene editing to generate host resistance by ablating viral entry receptors or cellular proteins that are required for completion of the viral life cycle. The solute carrier family 35 member A1 (SLC35A1) gene encodes a Golgi-localized CMP-sialic acid transporter that is a key step in the sialylation of glycoproteins. In this study, we used the CRISPR/Cas9 system to disrupt SLC35A1 in chicken DF-1 fibroblasts and evaluated the effect on sialic acid expression and susceptibility to different strains of AIV. Lectin staining and flow cytometry confirmed a significant reduction in α2,3-linked sialic acids in SLC35A1 knockout cells, while α2,6-linked sialic acids were absent in the cells regardless of genotype. Infection experiments with three avian influenza virus strains (H5N1/PR8, H5N2, and H7N1) revealed that SLC35A1 knockout reduced viral replication in a strain-specific manner. Knockout cells infected with H5N1/PR8 showed the greatest dependence on SLC35A1-mediated sialylation with decreased viral load at 24 hours post-infection (hpi) and 48 hpi compared to wildtype cells and no observable viral growth between the timepoints. Infection of knockout cells with H5N2 resulted in a modest decrease in viral load at both timepoints as well as absence of viral growth. On the other hand, infection of knockout cells with H7N1 resulted in decreased viral load only at 48 hpi compared to wildtype cells, but the amount of virus in knockout cultures increased from 24 hpi to 48 hpi. These results demonstrate that SLC35A1 is a key host factor that supports AIV entry via α2,3-linked sialic acids; however, viral dependency on this host factor may be confounded by strain.
Keywords: Avian influenza virus; CRISPR/Cas9; Genetic resistance; SLC35A1; Sialic acid.
. 2026 May 25;105(9):107178.
doi: 10.1016/j.psj.2026.107178. Online ahead of print.
Strain-specific responses of avian influenza virus to disruption of solute carrier family 35 member A1 (SLC35A1) in chicken cells
Heidi Liu[SUP] 1 [/SUP], Jéssica Moraes Cruvinel[SUP] 2 [/SUP], Wesley C Warren[SUP] 2 [/SUP], Wenjun Ma[SUP] 3 [/SUP], Paula R Chen[SUP] 4 [/SUP]
Affiliations
- PMID: 42241751
- DOI: 10.1016/j.psj.2026.107178
Avian influenza virus (AIV) poses a persistent threat to poultry health and food security, with conventional control measures offering limited protection. A promising alternative is the use of gene editing to generate host resistance by ablating viral entry receptors or cellular proteins that are required for completion of the viral life cycle. The solute carrier family 35 member A1 (SLC35A1) gene encodes a Golgi-localized CMP-sialic acid transporter that is a key step in the sialylation of glycoproteins. In this study, we used the CRISPR/Cas9 system to disrupt SLC35A1 in chicken DF-1 fibroblasts and evaluated the effect on sialic acid expression and susceptibility to different strains of AIV. Lectin staining and flow cytometry confirmed a significant reduction in α2,3-linked sialic acids in SLC35A1 knockout cells, while α2,6-linked sialic acids were absent in the cells regardless of genotype. Infection experiments with three avian influenza virus strains (H5N1/PR8, H5N2, and H7N1) revealed that SLC35A1 knockout reduced viral replication in a strain-specific manner. Knockout cells infected with H5N1/PR8 showed the greatest dependence on SLC35A1-mediated sialylation with decreased viral load at 24 hours post-infection (hpi) and 48 hpi compared to wildtype cells and no observable viral growth between the timepoints. Infection of knockout cells with H5N2 resulted in a modest decrease in viral load at both timepoints as well as absence of viral growth. On the other hand, infection of knockout cells with H7N1 resulted in decreased viral load only at 48 hpi compared to wildtype cells, but the amount of virus in knockout cultures increased from 24 hpi to 48 hpi. These results demonstrate that SLC35A1 is a key host factor that supports AIV entry via α2,3-linked sialic acids; however, viral dependency on this host factor may be confounded by strain.
Keywords: Avian influenza virus; CRISPR/Cas9; Genetic resistance; SLC35A1; Sialic acid.