Project description:The outbreak-causing monkeypox virus of 2022 (2022 MPXV) is classified as a clade IIb strain and phylogenetically distinct from prior endemic MPXV strains (clades I or IIa), suggesting that its virological properties may also differ. Here, we used human keratinocytes and induced pluripotent stem cell-derived colon organoids to examine the efficiency of viral growth in these cells and the MPXV infection-mediated host responses. MPXV replication was much more productive in keratinocytes than in colon organoids. We observed that MPXV infections, regardless of strain, caused cellular dysfunction and mitochondrial damage in keratinocytes. Notably, a significant increase in the expression of hypoxia-related genes was observed specifically in 2022 MPXV-infected keratinocytes. Our comparison of virological features between 2022 MPXV and prior endemic MPXV strains revealed signaling pathways potentially involved with the cellular damages caused by MPXV infections and highlights host vulnerabilities that could be utilized as protective therapeutic strategies against human mpox in the future.
Project description:Orthopox viruses, including monkeypox, multiply intracellularly and induce numerous changes in host genes expression. The virus target mainly humoral host response, and simultaneously, exploits other genes and functions to reproduce effectively. The goal of this experiment is to identify those host genes and functions that are essential for monkeypox virus replication. Mock infected control cells were treated and incubated identically to time point arms, except for virus exposure. Two time points of cells infected with monkeypox virus were harvested at 3, 7 hours post infection, and gene expression was assessed using microarray in all arms. The experiment was done in triplicate.
Project description:Orthopox viruses, including monkeypox, multiply intracellularly and induce numerous changes in host genes expression. The virus target mainly humoral host response, and simultaneously, exploits other genes and functions to reproduce effectively. The goal of this experiment is to identify those host genes and functions that are essential for monkeypox virus replication.
Project description:The soaring global monkeypox cases lead to a surge in demand for monkeypox vaccine, which far exceeds the supply. mRNA vaccine has achieved great success in prevention of coronavirus disease and holds promise against diverse pathogens. In this study, we generate a polyvalent lipid nanoparticle (LNP) mRNA vaccine candidate for monkeypox virus (MPXV) and evaluate its immunogenicity in animal models. This polyvalent MPXV mRNA vaccine candidate, MPXVac-097, encodes five 2022 MPXV targets that are important surface antigens. Three-dose (prime-boost-booster) MPXVac-097 vaccination elicits strong antibody response to A35R and E8L antigens, moderate response to M1R, but not B6R or A29, highlighting the differences in immunogenicity. Bulk T cell receptor (TCR) sequencing reveals preferential usage of VJ combinations and clonal expansion of peripheral T cells after MPXVac-097 vaccination. These data demonstrate initial feasibility of developing MPXV mRNA vaccine and pave the way for its future optimization.
