The host RNA polymerase II transcribes messenger RNAs with help of general initiation factors namely TFIIB, TFIID, TFIIE, TFIIF and TFIIH. They assemble on promoter DNA with polymerase II, creating a large multiprotein-DNA complex that supports efficient transcription.
Several viruses have evolved strategies to interfere with host transcription initiation factors. Inhibiting host transcription eventually leads to shutoff of host proteins expression and gives viruses transcripts a competitive edge for access to the cellular translation machinery. Preventing the expression of host proteins is also a strategy to counteract the antiviral response.The TATA-binding protein (TBP) is inhibited by HPV16 E7 protein or by adenovirus E1A protein, and it is cleaved by the poliovirus 3C protease. Thogoto virus ML protein interacts with host TFIIB and strongly inhibits IRF3 and NF-kappaB-regulated promoters. Varicella virus IE63 targets TFIIE, while Rift Valley fever virus targets TFIIH complex, showing the different strategies viruses use to downregulate host transcription.
Viruses inhibiting transcription initiation:
| Family | Virus | Viral protein | strategy of transcription initiation inhibition | references |
| Orthomyxoviridae, Thogotovirus | Thogoto virus | ML | Inhibition of TFIIB |
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| Papillomaviridae, alphapapillomavirus | HPV16 | E7 | Inhibition of TBP |
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| Picornaviridae | Poliovirus | 3C | Cleavage of TBP |
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| Bunyaviridae, Phlebovirus | Rift valley fever virus | NSs | Downregulates TFIIH subunit p62 |
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| Herpesviridae | Varicella virus | IE63 | Disruption of the transcriptional pre-initiation complex |
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| Adenoviridae, Mastadenovirus | Adenovirus | E1A | Inhibition of TBP |
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