Lab

Alec J Redwood's Lab

About the lab

Viral Gemonics Group.

The VGG seeks to understand the role that genetic diversity and multiple strain infection plays on host pathogen interaction using murine cytomegalovirus (MCMV) as a model.

The VGG is also investigating the use of MCMV as a vaccine vector for immunocontraception and the control of zoonotic infections

Featured research (2)

Murine cytomegalovirus (MCMV) is widely used as a model of human CMV (HCMV) infection. However, this model relies on strains of MCMV that have been serially passaged in the laboratory for over four decades. These laboratory strains have been cloned as bacterial artificial chromosomes (BACs), which permits rapid and precise manipulation. Low-passage strains of MCMV add to the utility of the mouse model of HCMV infection but do not exist as cloned BACs. This study describes the first such low-passage MCMV BAC. This BAC-derived G4 was initially attenuated in vivo , with subsequent full genomic sequencing revealing a novel spliced transcript required for salivary gland tropism. These data suggest that MCMV, like HCMV, undergoes tissue culture adaptation that can limit in vivo growth and supports the use of BAC clones as a way of standardizing viral strains and minimizing interlaboratory strain variation.
CMVs efficiently target MHC I molecules to avoid recognition by cytotoxic T cells. However, the lack of MHC I on the cell surface renders the infected cell susceptible to NK cell killing upon missing self recognition. To counter this, mouse CMV (MCMV) rescues some MHC I molecules to engage inhibitory Ly49 receptors. Here we identify a new viral protein, MATp1, that is essential for MHC I surface rescue. Rescued altered-self MHC I molecules show increased affinity to inhibitory Ly49 receptors, resulting in inhibition of NK cells despite substantially reduced MHC I surface levels. This enables the virus to evade recognition by licensed NK cells. During evolution, this novel viral immune evasion mechanism could have prompted the development of activating NK cell receptors that are specific for MATp1-modified altered-self MHC I molecules. Our study solves a long-standing conundrum of how MCMV avoids recognition by NK cells, unravels a fundamental new viral immune evasion mechanism, and demonstrates how this forced the evolution of virus-specific activating MHC I–restricted Ly49 receptors.

Lab head

Alec J Redwood
Department
  • Institute for Respiratory Health
About Alec J Redwood
  • Associate Professor Redwood works at the Univeristy of Western Australia. He is a Principle Research Fellow working on neoantigen vaccines for cancer immunotherapy. Dr Redwood is also the head of the Vaccines and Viral Immunity Group which focuses on cytomegaolovirus (CMV) immune evasion and genetics. A particular focus of this group is the use of CMV as a vaccine vector for multiple infectious agents and as a vector for cancer immunotherapy.

Members (2)

Baca Chan
  • University of Western Australia
Laura L Masters
  • University of Western Australia