HCMV, GLU4, and Diabetes

As we discussed in class, many viruses, though they don’t have their own machinery for movement, commandeer and manipulate the host cells’ machinery to induce movement, replicate, or simply create conditions more conducive to the virus.

One necessity for cell survival is the uptake of glucose. However, because glucose is polar, it can’t readily diffuse across the protective lipid bilayer, more specifically the hydrophobic region of the plasma membrane. Glucose specific membrane transporters are used to regulate transportation of glucose across the plasma membrane. In healthy cells, the glucose uptake is well mediated and steady levels of glucose uptake are maintained. However, cells infected with human cytomegalovirus (HCMV) upregulate the intake of glucose into host cells. HCMV is in the family herpesviridae and is an icosehedral, enveloped, double-stranded DNA virus. Because the virus stimulates rapid synthesis of proteins and rapid replication of the virus’s genome, the cell requires an increased energy supply to carry out the tasks.

Though the increase in glucose uptake has been known for years, researchers have recently investigated the mechanisms by which HCMV triggers the increase in glucose transport. What they discovered was a distinct increase in the expression of the glut4 gene and a increased activation of the GLU4 receptor. Acetyl CoA and growth factors are usually necessary for GLU4 upregulation; however, in this HCMV induced overproduction of GLU4, the need for Acetyl CoA and growth factor (liming factors) is bypassed. The overexpression also bypasses insulin signaling, increasing glucose transport dramatically.

The ability of the virus to infect the cell, take over its machinery, and then overcome its checks/limiting factors to avoid inhibition is amazing! The mechanisms by which viruses, specifically HCMV, increase glucose transport also seem reminiscent of some mechanisms of oncogenic viruses.

Another interesting aspect of this finding is its pertinence to diabetes. GLU4 is and insulin-dependant glucose transporter. Insulin decreases blood glucose by promoting glucose transport through GLU4. Diabetes is a chronic disorder where the patient has high levels of blood glucose cannot produce enough insulin. Since insulin stimulates glucose transport, a potential solution to the absence of insulin could be stimulating downstream GLU4. Perhaps by elucidating the mechanism of HCMV increased glcose transport, we can discover a more effective treatment for diabetes.

http://jvi.asm.org/cgi/content/full/85/4/1573

Alysha