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• W2125927306 abstract "ABSTRACT High-risk human papillomaviruses (HPVs) infect stratified epithelia to establish persistent infections that maintain low-copy-number episomes in infected basal cells. Amplification of viral genomes occurs upon keratinocyte differentiation, followed by virion synthesis. During persistent HPV infections, viral proteins act to evade surveillance by both innate and adaptive immune responses. One of the primary pathways regulating the innate immune response is the JAK/STAT pathway. Our studies indicate that the expression of STAT-1, but not other members of interferon (IFN)-stimulated gene factor 3 (ISGF-3) complex such as STAT-2 and IFN regulatory factor 9 (IRF9), is selectively suppressed by HPV proteins at the level of transcription. Both E6 and E7 oncoproteins independently suppress the expression of STAT-1, and mutational analyses indicate that the E6 targeting E6-associated protein (E6AP) is responsible for suppression. The levels of STAT-1 proteins increase upon differentiation of both normal and HPV-positive cells but are still significantly reduced in the latter cells. Transient restoration of STAT-1 levels in HPV-positive cells using recombinant retroviruses significantly impaired viral amplification upon differentiation while long-term increases abrogated maintenance of episomes. Similarly, increased levels of STAT-1 induced by gamma interferon treatment inhibited HPV genome amplification upon differentiation. Overall, our findings demonstrate that suppression of STAT-1 expression by HPV proteins is necessary for genome amplification and maintenance of episomes, suggesting an important role for this activity in viral pathogenesis." @default.
• W2125927306 created "2016-06-24" @default.
• W2125927306 creator A5007196678 @default.
• W2125927306 creator A5023408072 @default.
• W2125927306 creator A5067077329 @default.
• W2125927306 date "2011-09-15" @default.
• W2125927306 modified "2023-10-11" @default.
• W2125927306 title "Suppression of STAT-1 Expression by Human Papillomaviruses Is Necessary for Differentiation-Dependent Genome Amplification and Plasmid Maintenance" @default.
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• W2125927306 doi "https://doi.org/10.1128/jvi.05007-11" @default.
• W2125927306 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3165741" @default.
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• W2125927306 hasPublicationYear "2011" @default.
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