Genomic sequencing and characterization of cynomolgus macaque cytomegalovirus
Angie K Marsh1, David O Willer, Aruna P N Ambagala
1Department of Microbiology, Mount Sinai Hospital, Room 1484, 600 University Avenue, Toronto, ON, Canada.
Abstract:
Cytomegalovirus (CMV) infection is the most common opportunistic infection in immunosuppressed individuals, such as transplant recipients or people living with HIV/AIDS, and congenital CMV is the leading viral cause of developmental disabilities in infants. Due to the highly species-specific nature of CMV, animal models that closely recapitulate human CMV (HCMV) are of growing importance for vaccine development. Here we present the genomic sequence of a novel nonhuman primate CMV from cynomolgus macaques (Macaca fascicularis; CyCMV). CyCMV (Ottawa strain) was isolated from the urine of a healthy, captive-bred, 4-year-old cynomolgus macaque of Philippine origin, and the viral genome was sequenced using next-generation Illumina sequencing to an average of 516-fold coverage. The CyCMV genome is 218,041 bp in length, with 49.5% G+C content and 84% protein-coding density. We have identified 262 putative open reading frames (ORFs) with an average coding length of 789 bp. The genomic organization of CyCMV is largely colinear with that of rhesus macaque CMV (RhCMV). Of the 262 CyCMV ORFs, 137 are homologous to HCMV genes, 243 are homologous to RhCMV 68.1, and 200 are homologous to RhCMV 180.92. CyCMV encodes four ORFs that are not present in RhCMV strain 68.1 or 180.92 but have homologies with HCMV (UL30, UL74A, UL126, and UL146). Similar to HCMV, CyCMV does not produce the RhCMV-specific viral homologue of cyclooxygenase-2. This newly characterized CMV may provide a novel model in which to study CMV biology and HCMV vaccine development.
Insights
A new cynomolgus macaque cytomegalovirus (CyCMV) genome sequence provides a valuable animal model for studying human cytomegalovirus (CMV) infection and developing CMV vaccines.
Area of Science:
- Virology
- Genomics
- Immunology
Background:
- Cytomegalovirus (CMV) is a major opportunistic infection in immunocompromised individuals and a leading cause of infant developmental disabilities.
- Species-specific CMV necessitates relevant animal models for human CMV (HCMV) research and vaccine development.
Purpose of the Study:
- To present the genomic sequence of a novel nonhuman primate cytomegalovirus (CyCMV) from cynomolgus macaques.
- To evaluate CyCMV as a potential model for studying HCMV biology and vaccine development.
Main Methods:
- Isolation of CyCMV (Ottawa strain) from a healthy cynomolgus macaque.
- Next-generation Illumina sequencing of the viral genome.
- Bioinformatic analysis to identify open reading frames (ORFs) and compare genomic organization with other CMV strains.
Main Results:
- The complete CyCMV genome sequence (218,041 bp) was determined with 262 putative ORFs.
- Genomic organization is largely colinear with rhesus macaque CMV (RhCMV).
- CyCMV shares homology with HCMV genes, including four ORFs absent in RhCMV, and lacks a cyclooxygenase-2 homologue, similar to HCMV.
Conclusions:
- The characterized CyCMV genome provides a new resource for CMV research.
- CyCMV represents a promising animal model for investigating HCMV pathogenesis and advancing vaccine development efforts.
