Virological characteristics of SARS-CoV-2 Omicron BA.5.2.48 (preprint)

With the prevalence of sequentially-emerged sublineages including BA.1, BA.2 and BA.5, SARS-CoV-2 Omicron infection has transformed into a regional epidemic disease. As a sublineage of BA.5, the BA.5.2.48 outbreak and evolved into multi-subvariants in China without clearly established virological characteristics, especially the pathogenicity. Though reduced airborne transmission and pathogenicity of former Omicron sublineages have been revealed in animal models, the virological characteristics of BA.5.2.48 was unidentified. Here, we evaluated the in vitro and in vivo virological characteristics of two isolates of the prevalent BA.5.2.48 subvariant, DY.2 and DY.1.1 (a subvariant of DY.1). DY.2 replicates more efficiently than DY.1.1 in HelahACE2+ cells and Calu-3 cells. The A570S mutation (of DY.1) in a normal BA.5 spike protein (DY.2) leads to a 20% improvement in the hACE2 binding affinity, which is slightly reduced by a further K147E mutation (of DY.1.1). Compared to the normal BA.5 spike, the double-mutated protein demonstrates efficient cleavage and reduced fusogenicity. BA.5.2.48 demonstrated enhanced airborne transmission capacity in hamsters than BA.2. The pathogenicity of BA.5.2.48 is greater than BA.2, as revealed in K18-hACE2 rodents. Under immune selection pressure, DY.1.1 shows stronger fitness than DY.2 in hamster turbinates. Thus the outbreaking prevalent BA.5.2.48 multisubvariants exhibites divergent virological features.

Migrasomes deliver messages from migrating cells (preprint)

Migrasomes are newly discovered extracellular vesicles that can mediate communication between cells. These unique vesicles form exclusively at the rear of migrating cells with the help of a protein called TSPAN4. After they’re left behind, the migrasomes and their contents can be captured by nearby cells and affect the recipient cells’ behavior. They can also serve as “breadcrumb trails” that mark the paths of their migrating parent cells. Migrasomes participate in both health and disease. For example, they can dispose of damaged mitochondria to maintain healthy cells and they help establish left–right patterning in zebrafish embryos by releasing the protein CXCL12 to recruit dorsal forerunner cells (DFCs). However, migrasomes can also deliver molecules that promote tumor growth and metastasis and migrasomes released from platelets promote blood clotting after SARS-CoV-2 infection. Furthermore, migrasomes can facilitate an eye condition called proliferative vitreoretinopathy that leads to retinal detachment and blindness. Better characterization of the contents and roles of migrasomes will help us understand these newly identified vesicles and reveal how they can be leveraged to diagnose and treat diseases.