Oliver Oakley, Ph.D.
Assistant Professor, Clinical Laboratory Science
Concurrent Infection with P.carinii and CMV in mice
Despite the practice of antimicrobial prophylaxis, CMV and P. carinii (PC) pneumonia (PCP) are both leading cause of morbidity and mortality in patients with immunocompromised states resulting from malignancies, solid organ and bone marrow transplants, or AIDS. In addition, newborns with congenital or perinatal CMV infection also suffer from concomittent PCP. The interaction of these pathogens and their effects on host immune response is not clearly understood. Therefore, it is important to better understand the pathophysiology of PC and CMV dual infection.
Mechanisms of Exacerbation of GVHD by Murine CMV in BMT
Bone marrow transplantation (BMT) is being used for the treatment of a growing number of life threatening illnesses from leukemia to aplastic anemia. While many lives have been saved, the procedure is associated with serious risks, notably opportunistic infections and the development of graft versus host disease (GVHD). Cytomegalovirus (CMV) infection has been the most prevalent infectious agent found in BMT patients, and, prior to the use of preemptive ganciclovir therapy, was a major cause of death after BMT. The highest risk scenario for CMV occurs when a sero-positive recipient (with latent viral infection) receives bone marrow from a sero-negative donor, thus transplanting a “CMV-naïve” immune system into a host in whom the virus can reactivate during periods of immunosuppression. It is now well recognized that CMV infection can exacerbate GVHD after allogeneic BMT. However, the precise mechanisms by which CMV worsens GVHD remain incompletely defined.
Re-activation of Murine Cytomegalovirus in BMT and its Impact on Pneumonitis
Bone marrow transplantation (BMT) is being used extensively for the treatment of numerous life threatening diseases from leukemia to aplastic anemia. Whilst the procedure can offer life saving relief, it is also associated with serious risks, most notably opportunistic infections, including cytomegalovirus (CMV) graft-versus-host disease (GVHD) and numerous pulmonary complications. Interstitial pneumonia (IP) is the most common manifestation of CMV morbidity in BMT patients despite adequate treatment. The precise mechanism by which re-activating latent virus worsens IP is still unclear. My research focus is to define the mechanisms by which prior CMV infection causes exacerbation of IP in a murine model of allogeneic BMT.