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Human cytomegalovirus is more complex than predicted

Scientists have discovered a record number of proteins for one of the largest and most complex viruses, the highly infectious and stealthy human cytomegalovirus, a team from Pacific Northwest National Laboratory and Oregon Health & Science University reports in the October Journal of Virology.

Human cytomegalovirus, or HCMV, is a member of the herpesvirus family. HCMV infects and persists for life in 50 to 85 percent of Americans 40 years and older. Few know they are infected and show no ill effects, but HCMV is the leading viral cause of birth defects and is a serious threat to transplant and AIDS patients and others with a compromised immune system.

“Our labs identified the viral and host proteins that compose the HCMV virion,” said Jay Nelson, Ph.D., director of the OHSU Vaccine and Gene Therapy Institute (VGTI) and a study co-author. “By identifying the proteins in the HCMV virion, we hope to develop new treatments for these at-risk patients.”

The team discovered 71 proteins in mature HCMV, double the number previously identified. HCMV may express as many as 200 proteins at various points in its life cycle. By comparison, adenovirus, responsible for the common cold, contains about 11 proteins.

“The proteins may not all be present at the same time,” said Susan Varnum, a PNNL staff scientist and the study's co-lead author, “but we believe we're seeing most that are expressed in the mature virus.”

The researchers also were surprised to find that when a cell is infected, the HCMV virus incorporates into itself a huge number of that host cell's proteins, “some of which were as abundant as viral proteins, demonstrating the complexity of this common virus,” explained Dan Streblow, Ph.D., a research assistant professor of molecular microbiology and immunology in Nelson's lab. “In addition, one of these host cell proteins pointed us to sites in the cell where viruses are assembled.”

The prevalence of host proteins in the virus, Varnum said, might also suggest how the virus avoids detection by the immune system—that it's using the body's own cellular proteins as camouflage.

Before this study, a comprehensive analysis of the proteins that constitute the HCMV virion had not been possible without the development of new proteomics technologies in the PNNL lab of Richard Smith, a Battelle Fellow and study co-author. To conduct this research, scientists used proteomics instruments and approaches unavailable elsewhere that combine the high resolution separations of proteins with their identification at the same time, using a powerful mass spectrometer developed at PNNL.