Translating Science into Survival: Report on the Sixth International Cancer Immunotherapy Conference.

From September 28 to October 1, 2022, in New York City, the Sixth International Cancer Immunotherapy Conference was hosted jointly by the Cancer Research Institute (CRI), the American Association for Cancer Research, and the European Network for Cancer Immunotherapy. The four-day event covered the latest advances in cancer immunology and immunotherapy.

Serotype-specific restriction of wild-type adenoviruses by the cellular Mre11-Rad50-Nbs1 complex.

During viral replication in the nucleus, the DNA genomes of adenoviruses are accessible to cellular DNA-binding proteins. Human adenovirus type 5 (Ad5) targets the cellular Mre11-Rad50-Nbs1 complex (MRN) to evade detection by the DNA damage response (DDR). Ad5 mutants that cannot target MRN have reduced viral propagation.

Identifying Host Factors Associated with DNA Replicated During Virus Infection.

Viral DNA genomes replicating in cells encounter a myriad of host factors that facilitate or hinder viral replication. Viral proteins expressed early during infection modulate host factors interacting with viral genomes, recruiting proteins to promote viral replication, and limiting access to antiviral repressors. Although some host factors manipulated by viruses have been identified, we have limited knowledge of pathways exploited during infection and how these differ between viruses.

Take your PIKK: tumour viruses and DNA damage response pathways.

Viruses regulate cellular processes to facilitate viral replication. Manipulation of nuclear proteins and pathways by nuclear replicating viruses often causes cellular genome instability that contributes to transformation. The cellular DNA damage response (DDR) safeguards the host to maintain genome integrity, but DNA tumour viruses can manipulate the DDR to promote viral propagation.

Adenovirus Core Protein VII Downregulates the DNA Damage Response on the Host Genome.

Viral manipulation of cellular proteins allows viruses to suppress host defenses and generate infectious progeny. Due to the linear double-stranded DNA nature of the adenovirus genome, the cellular DNA damage response (DDR) is considered a barrier to successful infection. The adenovirus genome is packaged with protein VII, a virally encoded histone-like core protein that is suggested to protect incoming viral genomes from detection by the cellular DNA damage machinery.

An Intrinsically Disordered Region of the DNA Repair Protein Nbs1 Is a Species-Specific Barrier to Herpes Simplex Virus 1 in Primates.

Humans occasionally transmit herpes simplex virus 1 (HSV-1) to captive primates, who reciprocally harbor alphaherpesviruses poised for zoonotic transmission to humans. To understand the basis for the species-specific restriction of HSV-1 in primates, we simulated what might happen during the cross-species transmission of HSV-1 and found that the DNA repair protein Nbs1 from only some primate species is able to promote HSV-1 infection. The Nbs1 homologs that promote HSV-1 infection also interact with the HSV-1 ICP0 protein.

A core viral protein binds host nucleosomes to sequester immune danger signals.

Viral proteins mimic host protein structure and function to redirect cellular processes and subvert innate defenses. Small basic proteins compact and regulate both viral and cellular DNA genomes. Nucleosomes are the repeating units of cellular chromatin and play an important part in innate immune responses.

Recruitment of Brd4 to the human papillomavirus type 16 DNA replication complex is essential for replication of viral DNA.

Replication of the human papillomavirus (HPV) DNA genome relies on viral factors E1 and E2 and the cellular replication machinery. Bromodomain-containing protein 4 (Brd4) interacts with viral E2 protein to mediate papillomavirus (PV) genome maintenance and viral transcription. However, the functional role of Brd4 in the HPV life cycle remains to be clearly defined.