Sunday, December 8, 2013

Levels of a common, chronic virus (TTV) reflects the immune competence of transplant recipients

Successful organ transplantation requires careful immune suppression: enough to block the rejection of transplant while permitting host defense against infectious microbes.   Viruses that are not cleared by our immune systems, are common in healthy people, and can complicate transplantation include cytomegalovirus (CMV) and Torque teno virus (TTV), which was first described in 1997 [review].  TTV is a small (3.8 kb), single-stranded, transfusion transmitted DNA virus, representative of a highly diverse family of anelloviruses 

The authors examined the influence of immune-suppressive drugs (e.g., tacrolimus, mycophenolate mofitil, cyclosporine) and the anti-CMV drug valgancyclovir on chronic, endogenous microbes.  From 96 heart or lung transplant recipients they collected 656 blood samples over time, some up to a year post-transplant, removed the cells, and identified remaining DNA by sequencing.  They found that 0.12% matched viral or bacterial or fungal sequences.  They validated some ‘hits’ with quantitative PCR.  Control preparations using water or bacteriophage demonstrated no relevant artifacts or contamination.  

They found that treatment with valgancyclovir reduced herpesviruses, including CMV, but dramatically increased the relative and absolute levels of anelloviruses, including TTVs (fig. 2, 3, 4).   Moreover, those patients who did not reject their transplants tended to have a greater increase in anelloviruses (Fig. 5A, shown; rejecting patients plotted in red).  The authors conclude that anellovirus levels might be used to monitor immune competence.   Focosi et al. made a related observation following autologous stem cell transplantation

 Cell. 2013 Nov 21;155(5):1178-87. Temporal response of the human virome to immunosuppression and antiviral therapy.  De Vlaminck I, Khush KK, Strehl C, Kohli B, Luikart H, Neff NF, Okamoto J, Snyder TM, Cornfield DN, Nicolls MR, Weill D, BernsteinD, Valantine HA, Quake SR.