Poxvirus Biology

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications & trials

Abstract

In FY23, we continued our studies on the virulence of MPXV using the CAST mouse model that we had developed previously. Representative members of MPXV clades I, IIa and IIb were injected intranasally or intraperitoneally and the morbidity and survival were determined. We found that the order of virulence was clade I > clade IIa > clade IIb. The low virulence of clade IIb MPXV was unanticipated. In addition, individual and groups of genes in a clade I strain were replaced with the corresponding genes of the less virulent and less transmissible clade IIa strain and the effects on morbidity and survival of the clade I strain determined. These experiments are ongoing. In FY23 we used AlphaFold2 to predict the structure of all 214 orthopoxvirus proteins and their origins were determined by significant similarity to proteins encoded by cellular genes. High quality structures were obtained for 194 orthopoxvirus proteins of which 179 had cellular counterparts. Many of the viral proteins had lost catalytic functions indicative of altered function. We continued studies on the VACV entry-fusion proteins and determined the importance of N-myristoylation of the proteins A16, G9 and L1. While this modification was essential for L1, it had a lesser role for A16 and G9.