Integrative analyses reveal novel strategies in HPV11,-16 and -45 early infection.
The interaction between human papillomavirus (HPV) and host cells is not well understood. We investigate the early stage of HPV infections by global expression profiling in a cell model, in which HaCaT cells were transfected with HPV11, HPV16 or HPV45 genomes. We report the differential expression of genes not previously implicated in HPV biology, such as the PSG family and ANKRD1, and of genes implicated in the biology of other viruses, e.g. MX1, IFI44 and DDX60. Carcinogenesis-related genes, e.g. ABL2, MGLL and CYR61, were upregulated by high-risk HPV16 and -45. The integrative analysis revealed the suppression of DNA repair by HPV11 and -16, and downregulation of cytoskeleton genes by all HPV types. Various signalling pathways were affected by the HPVs: IL-2 by HPV11; JAK-STAT by HPV16; and TGF-β, NOTCH and tyrosine kinase signalling by HPV45. This study uncovered novel strategies employed by HPV to establish infection and promote uncontrolled growth.
The Bioinformatics Centre, Department of Biology and Biomedical Research and Innovation Centre, Copenhagen University, Ole Maaloes Vej 5, 2200Copenhagen, Denmark. bok@binf.ku.dk
Bogumil
B
Kaczkowski
Maria
M
Rossing
Ditte K
DK
Andersen
Anita
A
Dreher
Marya
M
Morevati
Melissa A
MA
Visser
Ole
O
Winther
Finn Cilius
FC
Nielsen
Bodil
B
Norrild
D002460:Cell Line; D002472:Cell Transformation, Viral / Q000235:genetics*; D019295:Computational Biology / Q000379:methods; D003588:Cytopathogenic Effect, Viral; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D053263:Gene Regulatory Networks; D054884:Host-Pathogen Interactions; D052140:Human papillomavirus 11 / Q000235:genetics*; D052162:Human papillomavirus 16 / Q000235:genetics*; D006801:Humans; D027383:Papillomaviridae / Q000235:genetics*; D060066:Protein Interaction Maps; D014779:Virus Replication