Lrp1 is a host entry factor for Rift Valley fever virus (RVFV)

Lrp1 is a member of the low-density lipoprotein (LDL) receptor family, and they play roles in lipid metabolism and in several endocytic and inflammatory signalling pathways. Screening of genome-wide CRISPR/Cas9 libraries revealed that Lrp1, together with its modulators, RAP and GRP94, are essential host factors for the virulence of RVFV. Lrp1 is conserved across species and different cell types, which could explain the wide host range of the zoonotic virus. Knockout of Lrp1, RAP and GRP94 significantly reduced infection by both the pathogenic and attenuated strains of RVFV. Reduced infection was observed in both cell lines and in primary mouse embryonic fibroblasts. The direct interaction between Lrp1 and glycoprotein was analyzed and found to play an important role in the infection process. Targeting Lrp1 offers a promising therapeutic target against RVFV, which has a pandemic potential.
(MRM)

Human Respiratory Syncytial Virus Infection in a Human T Cell Line is Hampered at Multiple Steps

Human Respiratory Syncytial Virus (HRSV) is a leading cause of acute respiratory infections in humans, more so in infants, the elderly and immunocompromised individuals. HRSV-cell interactions have been studied using epithelial cells. HRSV-cell interaction was studied using lymphoid cells. Although the viral-cell attachment of HRSV to Hep-2 and A3.01 cells is only slightly different, viral genome replication and protein production is greatly reduced in A3.01 cells compared to Hep-2 cells. While there is a clear colocalization between HRSV F protein and Golgi markers in Hep-2 cells, HRSV F protein shows partial colocalization with Golgi markers in A3.01 cells. Although HRSV proteins were readily detected in intracellular compartments of A3.01 cells, very little accumulation of HRSV products was seen at the plasma membrane, which resulted in a lower filament production in these cells. This study suggests that viral replication in A3.01 cells is altered at several stages, including virus-cell fusion, formation of defective inclusion bodies, impaired viral protein production and lack of effective trafficking of viral proteins to virus assembly sites.
(MRM)