Biology subjects

Torres-Gonzalez, E.

Publications and source records attributed to Torres-Gonzalez, E..

4 recordsLinked to original sources

bioRxiv2026

Interferon-α and -β subtypes have temporally distinct roles in containing viral spread and protecting vital organs.

Type I interferons (IFN-Is), including a single IFN-{beta} and over a dozen IFN-s, induce the anti-viral state. In vitro, IFN-{beta} transcription requires the assembly of the "enhanceosome" composed of the constitutive transcription factors NF-{kappa}B and AP-1, and either constitutive IRF3 or IFN-I-inducible IRF7. IRF3 and IRF7 transcribe mouse IFN-4 and human IFN-1/13. Only IRF7 transcribes other IFN-s. How IFN-I subtype multiplicity and their differential constitutive/IFN-I-inducible versus only IFN-I-inducible transcription help control viruses in vivo remains unknown. Using novel genetically modified mice, we demonstrate that most or all IFN-I subtypes, regardless of their transcriptional control, are necessary to curb the systemic dissemination of lymph-borne ectromelia virus (ECTV) but do not necessarily suppress ECTV or West Nile Virus (WNV) replication in the liver or the brain, or promote survival to their infection. Individually, the most critical IFN-I subtype to survive ECTV and WNV infections is IFN-{beta}. IFN-4 potentiates IFN-{beta} but is not essential. PRDII, the IFN-{beta} promoters NF-{kappa}B binding site, which is required for enhanceosome assembly, is dispensable for in vivo IFN-{beta} production but complements IRF7-IFN-{beta} transcription to restrain ECTV and WNV. IFN-{beta} alone protects IFN--deficient mice from ECTV but not from WNV lethality. Control of WNV replication in the brain successively requires IFN-, IFN-{beta}, and then PRDII-dependent IFN-{beta}, suggesting that brain protection requires IFN-I production by various cell types and pathways. Thus, contrary to the prevailing view, in vivo, IFN-{beta} does not function earlier than IFN-, and IFN-I subtypes non-redundantly cooperate to restrain viruses in the periphery and in vital organs.

immunology↗

bioRxiv2025

Nuclear Mitochondrial Sequences in Great Ape Telomere-to-Telomere Genomes

Mitochondrial sequences have integrated into the nuclear genome since the origin of eukaryotes. Recent insertions that retain homology to extant mitochondrial DNA (mtDNA), termed NUMTs, confound mtDNA sequence analysis. Here, we used great ape Telomere-to-Telomere (T2T) genomes to study NUMTs in bonobo, chimpanzee, human, gorilla, and Bornean and Sumatran orangutans. A phylogeny based on shared and lineage-specific NUMTs accurately recapitulated the great ape species tree topology. NUMTs were enriched at non-functional non-repetitive regions of the nuclear genome, and depleted within enhancers and coding sequences, suggesting negative selection. We validated the presence of a 76-kilobase-long heterozygous NUMT in chimpanzee, which was larger than any other NUMT observed in great apes, and found that dozens of NUMTs on the Pan Y chromosome expanded together with palindromes. Our study highlights NUMTs as a dynamic evolutionary force contributing to shaping ape genomes, and is valuable for characterizing mtDNA in great apes.

genomics↗

bioRxiv2020

Human papillomavirus 16 positive cervical cancer in Guatemala: The D2 and D3 sublineages differ in integration rate and age of diagnosis

Human papillomavirus (HPV) 16 displays substantial sequence variation; four HPV16 lineages (A, B, C, D) have been described, as well as multiple sub-lineages. To identify molecular events associated with HPV16 carcinogenesis we evaluated viral variation, the integration of HPV16, and somatic mutation in 96 cervical cancer samples from Guatemala. A total of 64% (60/94) of the samples had integrated HPV16 sequences, and integration was associated with an earlier age of diagnosis (P=0.0007) and pre-menopausal disease. HPV16 integration sites were broadly distributed in the genome but in one tumor, HPV16 integrated into the promoter of the interferon regulatory factor 4 (IRF4) gene, which plays an important role in the regulation of the interferon response to viral infection. The HPV16 D2 and D3 sub-lineages were found in 23% and 30% of the tumors, respectively and were significantly associated with adenocarcinoma. D2-positive tumors had a higher rate of integration (P=0.011), earlier age of diagnosis (P=0.012), and a lower rate of somatic mutation (P=0.03). Whereas D3-positive tumors are less likely to integrate, have later age-of-diagnosis, and a higher rate of somatic mutation. In conclusion, Guatemalan cervical tumors have a high frequency of the very high-risk HPV16 D2 and D3 sub-lineages and cervical cancer patients with these variants of HPV16 differ in histology, age of- diagnosis, integration, and somatic mutation frequency. In summary, related lineages of HPV16 have different features of oncogenicity.

cancer biology↗

bioRxiv2019

High prevalence of precocious menarche in Puerto Barrios, Guatemala

BackgroundAge of menarche is variable between women with a median age of 14 years old worldwide, and averages ranging from 12-13 years old in developed countries to 15-16 years old in low and middle-income countries. Precocious menarche, occurring before age 11, is rare, with a prevalence of 1.4 to 2.3% in most worldwide populations. Precocious menarche is poorly understood but is associated with early puberty and is a risk factor for pre-teen birth. In studying HPV prevalence in Latin America, we identified a community with a very high rate of precocious menarche. Objective(s)Describe the patterns of precocious menarche in Guatemala. Study DesignReproductive histories were collected from 3385 cancer-free women at the time of routine Pap smear from 4 sites in Guatemala including hospitals in Guatemala City and Puerto Barrios, Izabal. Statistical analyses included determination of the age-specific prevalence of menarche and linear regression to determine the effect of year of birth, study site, number of births and miscarriages, on the age at menarche. ResultsCompared with a low prevalence of precocious menarche observed in Guatemala City (3.1%, 88/2834), we observed a high prevalence of precocious menarche in the city of Puerto Barrios, Izabal, Guatemala (88%, 486/551). We observed a high prevalence of precocious menarche in Puerto Barrios across all age groups. In contrast in Guatemala City, the median age at menarche declined from the age of 14 in 50-60-year-old women to 13 in women under 40 years of age. Hospital records show that the occurrence of both miscarriage and pregnancy under age 14 is substantially higher in Izabal. In addition, the main public hospital in Puerto Barrios accounts for a high fraction of the early pregnancies and miscarriages seen in Guatemala. ConclusionsIn Puerto Barrios, Izabal, Guatemala, the prevalence of menarche before age 11 is dramatically elevated compared to Guatemala City and substantially higher than other worldwide populations. We observed precocious menarche in Puerto Barrios in all age groups examined, indicating that this condition has been common for decades. This finding is supported by the comparatively higher occurrence of early pregnancy and miscarriage in Puerto Barrios compared with Guatemala City. The cause is unknown, but precocious menarche is associated with adverse reproductive outcome in young women and warrants further investigation.

epidemiology↗