Dr. Ravit Boger is an assistant professor, division of pediatric infectious diseases at Johns Hopkins. In recent years, she worked with her mentors Dr. Hayward and Dr. Pass on CMV strain variation. Through this K08 award, she will conduct translational research to determine the molecular epidemiology of primary CMV infection in healthy adults, and gain expertise in molecular epidemiology and virology, advanced skills in genome sequencing, real-time PCR, and the responsible conduct of research. Molecular techniques have detected numerous CMV strains in the population. Primary human CMV infection is traditionally believed to be caused by a single strain, and isolation of multiple strains has been considered proof of re-infection. While specific populations (transplant recipients, AIDS patients, children in day care, etc.) may over time be re-infected with multiple CMV strains, no previous studies have determined whether initial CMV infection in healthy subjects involves multiple strains. Previously, we identified multiple CMV strains from tissues of CMV-induced fetal demise, yet only a single strain was identified from cultured isolates of CMV-infected live infants. It is unclear whether this difference has clinical significance or is related to direct sequencing from tissue as opposed to sequencing after selection of preferential isolates in culture. This application aims to characterize strain heterogeneity during primary CMV infection in a cohort of healthy women who participated in a randomized double-blind gB vaccine trial and who seroconverted during follow up. Dr. Boger will analyze hypervariable CMV genes from serial samples of original body fluids and cultured isolates that have been obtained from these individuals during primary CMV infection and 6-24 months afterwards. She will also determine whether vaccine-induced immunity affects the acquisition of strains over time, and whether specific genotypes are associated with viral load in various body fluids. This study will help understand the extent to which strain diversity can be used as evidence of re-infection and how natural CMV infection leads to broad immunity to the virus. This work is relevant to public health since strain variation may be responsible for increased virulence of some infections and because the phenomenon of strain variation may impact on the development of effective vaccine aimed at prevention of congenital CMV infection.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08AI074907-04
Application #
8111888
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Program Officer
Beisel, Christopher E
Project Start
2008-09-01
Project End
2012-07-31
Budget Start
2011-08-01
Budget End
2012-07-31
Support Year
4
Fiscal Year
2011
Total Cost
$136,113
Indirect Cost
Name
Johns Hopkins University
Department
Pediatrics
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Arav-Boger, Ravit (2015) Strain Variation and Disease Severity in Congenital Cytomegalovirus Infection: In Search of a Viral Marker. Infect Dis Clin North Am 29:401-14
Arav-Boger, Ravit; Wojcik, Genevieve L; Duggal, Priya et al. (2012) Polymorphisms in Toll-like receptor genes influence antibody responses to cytomegalovirus glycoprotein B vaccine. BMC Res Notes 5:140
Forman, Michael; Valsamakis, Alexandra; Arav-Boger, Ravit (2012) Dried urine spots for detection and quantification of cytomegalovirus in newborns. Diagn Microbiol Infect Dis 73:326-9
Kapoor, Arun; Cai, Hongyi; Forman, Michael et al. (2012) Human cytomegalovirus inhibition by cardiac glycosides: evidence for involvement of the HERG gene. Antimicrob Agents Chemother 56:4891-9
He, Ran; Park, Kyoungsook; Cai, Hongyi et al. (2012) Artemisinin-derived dimer diphenyl phosphate is an irreversible inhibitor of human cytomegalovirus replication. Antimicrob Agents Chemother 56:3508-15
He, Ran; Sandford, Gordon; Hayward, Gary S et al. (2011) Recombinant luciferase-expressing human cytomegalovirus (CMV) for evaluation of CMV inhibitors. Virol J 8:40
He, Ran; Mott, Bryan T; Rosenthal, Andrew S et al. (2011) An artemisinin-derived dimer has highly potent anti-cytomegalovirus (CMV) and anti-cancer activities. PLoS One 6:e24334
Murthy, Suchetha; Hayward, Gary S; Wheelan, Sarah et al. (2011) Detection of a single identical cytomegalovirus (CMV) strain in recently seroconverted young women. PLoS One 6:e15949
Arav-Boger, Ravit; He, Ran; Chiou, Chuang-Jiun et al. (2010) Artemisinin-derived dimers have greatly improved anti-cytomegalovirus activity compared to artemisinin monomers. PLoS One 5:e10370