Biology subjects

Soleimanpour, M.

Publications and source records attributed to Soleimanpour, M..

3 recordsLinked to original sources

bioRxiv2026

Deconvolution of HIV-1 Mutational Signatures Reveals Dominant and Donor-Specific APOBEC3-Associated Mutagenesis Across Anatomical Compartments

HIV-1 persists across multiple anatomical compartments, yet the mutational processes shaping viral diversity within these reservoirs remain incompletely understood. We investigated HIV-1 mutational signatures across blood, spleen, gut, and brain tissues from 21 people with HIV enrolled in the Last Gift rapid autopsy program. Mutations in single-genome HIV-1 env DNA sequences were quantified by trinucleotide context and deconvolved using non-negative matrix factorization. Two APOBEC3-associated signatures were resolved and together accounted for approximately 50% of all mutations; this contribution remained stable after normalization by the number of potential APOBEC3 target sites. Normalization further revealed a minor signature consistent with methylation-induced cytosine deamination. Mutational patterns were driven primarily by donor identity rather than anatomical compartment. Identical APOBEC3-hypermutated sequences were recovered across brain, gut, and blood, consistent with clonal expansion and trafficking of infected cells. These findings establish APOBEC3 activity as a major contributor to HIV-1 mutagenesis across tissue reservoirs and demonstrate that APOBEC3-associated mutagenesis is strongly donor-specific.

genomics↗

bioRxiv2026

Deciphering the Network Architecture of APOBEC3-Driven Mutagenesis in HPV-Positive Head and Neck Cancers

APOBEC3A (A3A) and APOBEC3B (A3B) are cytosine deaminases that restrict viral infection and can also mutate the host genome. In human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC), expression of both enzymes is elevated, but bulk sequencing averages their effects across mixed cell populations. Here we profile single cells from HPV16-positive HNSCC tumors and matched normal tissue. We find that the APOBEC3 (A3) single base substitution mutational signature, SBS2, is enriched in cells expressing more A3A than A3B, whereas copy number alteration (CNA) burden is enriched in cells expressing more A3B than A3A. Tumor versus normal co-expression networks identify the A3 interactors RALY and HNRNPA2B1 as candidate A3 activators. We found that SBS2 and CNA mark the maintenance and productive stages of HPV16 lifecycle, and their ratio may offer a molecular estimate of tumor age. The neoantigens from immune-visible SBS2-HIGH and immune-evasive CNA-HIGH cells identify candidates for mRNA vaccines matched to a tumor's viral state.

cancer biology↗

bioRxiv2026

APOBEC3G Splicing Defects in Nonhuman Primate Models Result in Disparate Viral Mutational Profiles Relative to Humans

Nonhuman primates (NHPs), particularly macaques, are indispensable models for studying human infectious diseases due to their close immunological and physiological similarities. Understanding species-specific molecular differences is essential for maximizing the translational value of these models. Here we report that APOBEC3G (A3G), a potent antiviral restriction factor and the major source of genetic variations in HIV, exhibits a widespread mRNA splicing defect in the Cercopithecinae subfamily, which includes the commonly used NHP models. Driven by intronic polymorphisms, this splicing defect substantially reduces A3G protein levels and consequently results in a markedly reduced A3G-mediated mutation signatures, fewer defective viral genomes, and greater viral diversification in SIV compared to HIV. This species-specific effect is not restricted to lentiviruses: reduced A3G signatures have also been reported in simian foamy virus and simian T-cell leukemia virus, suggesting broader effects across primate retroviruses. These findings reveal a lineage-specific alteration in a major antiviral restriction factor, with important implications for viral restriction, evolution, drug resistance, and immune evasion. They also highlight the importance of incorporating naturally occurring genetic variation into NHP model selection to improve the reproducibility, translational fidelity, and biological relevance of preclinical research.

genomics↗