Abstract
BackgroundCo-infection of multiple genotypes of human papillomavirus (HPV) is commonly observed among women with abnormal cervical cytology, but how different HPVs interact with each other in the same cell is not clearly understood. A previous study using cultured keratinocytes revealed that genome replication of one HPV type is inhibited by co-existence of the genome of another HPV type, suggesting that replication interference occurs between different HPV types when co-infected; however, molecular mechanisms underlying inter-type replication interference have not been fully explored.MethodsReplication interference between two most prevalent HPV types, HPV16 and HPV18, was examined in HPV-negative C33A cervical carcinoma cells co-transfected with genomes of HPV16 and HPV18 together with expression plasmids for E1/E2 of both types. Levels of HPV16/18 genome replication were measured by quantitative real-time PCR. Physical interaction between HPV16/18 E1s was assessed by co-immunoprecipitation assays in the cell lysates.ResultsThe replication of HPV16 and HPV18 genomes was suppressed by co-expression of E1/E2 of heterologous types. The interference was mediated by the heterologous E1, but not E2. The oligomerization domain of HPV16 E1 was essential for HPV18 replication inhibition, whereas the helicase domain was dispensable. HPV16 E1 co-precipitated with HPV18 E1 in the cell lysates, and an HPV16 E1 mutant Y379A, which bound to HPV18 E1 less efficiently, failed to inhibit HPV18 replication.ConclusionsCo-infection of a single cell with both HPV16 and HPV18 results in replication interference between them, and physical interaction between the heterologous E1s is responsible for the interference. Heterooligomers composed of HPV16/18 E1s may lack the ability to support HPV genome replication.
Highlights
Co-infection of multiple genotypes of human papillomavirus (HPV) is commonly observed among women with abnormal cervical cytology, but how different HPVs interact with each other in the same cell is not clearly understood
C33A cells were transfected with circularized full-genome DNA of HPV16 (Figure 2A) or HPV18 (Figure 2B) together with increasing amounts of pF16E1 and pF16E2, or pF18E1 and pF18E2
Compared to the replication levels for HPV16 or HPV18 supported by the homologous E1/E2, replication supported by the heterologous E1/E2 was relatively inefficient
Summary
Co-infection of multiple genotypes of human papillomavirus (HPV) is commonly observed among women with abnormal cervical cytology, but how different HPVs interact with each other in the same cell is not clearly understood. Human papillomavirus (HPV) has a circular doublestranded DNA genome of approximately 8 kilo basepairs packaged in a capsid composed of two proteins L1 and L2 [1]. The life cycle of HPV is tightly linked to the differentiation of host epithelial cells. HPV infects basal cells of stratified epithelia through small lesions, in which the viral genome is maintained as episomes without expressing capsid genes and is passed on to daughter cells. When the host cells initiate epithelial differentiation, the HPV genome starts to replicate, and infectious virions are produced and released from terminally differentiated cornified cells [3].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
