Due to the stringent population bottleneck that occurs during sexual HIV-1 transmission, systemic infection is typically established by a limited number of founder viruses. Elucidation of the precise forces influencing the selection of founder viruses may reveal key vulnerabilities that could aid in the development of a vaccine or other clinical interventions. Here, we utilize deep sequencing data and apply a genetic distance-based method to investigate whether the mode of sexual transmission shapes the nascent founder viral genome. Analysis of 74 acute and early HIV-1 infected subjects revealed that 83% of men who have sex with men (MSM) exhibit a single founder virus, levels similar to those previously observed in heterosexual (HSX) transmission. In a metadata analysis of a total of 354 subjects, including HSX, MSM and injecting drug users (IDU), we also observed no significant differences in the frequency of single founder virus infections between HSX and MSM transmissions. However, comparison of HIV-1 envelope sequences revealed that HSX founder viruses exhibited a greater number of codon sites under positive selection, as well as stronger transmission indices possibly reflective of higher fitness variants. Moreover, specific genetic “signatures” within MSM and HSX founder viruses were identified, with single polymorphisms within gp41 enriched among HSX viruses while more complex patterns, including clustered polymorphisms surrounding the CD4 binding site, were enriched in MSM viruses. While our findings do not support an influence of the mode of sexual transmission on the number of founder viruses, they do demonstrate that there are marked differences in the selection bottleneck that can significantly shape their genetic composition. This study illustrates the complex dynamics of the transmission bottleneck and reveals that distinct genetic bottleneck processes exist dependent upon the mode of HIV-1 transmission.
OBJECTIVE Planum sphenoidale (PS) and tuberculum sellae (TS) meningiomas cause visual symptoms due to compression of the optic chiasm. The treatment of choice is surgical removal with the goal of improving vision and achieving complete tumor removal. Two options exist to remove these tumors: the transcranial approach (TCA) and the endonasal endoscopic approach (EEA). Significant controversy exists regarding which approach provides the best results and whether there is a subset of patients for whom an EEA may be more suitable. Comparisons using a similar cohort of patients, namely, those suitable for gross-total resection with EEA, are lacking from the literature. METHODS The authors reviewed all cases of PS and TS meningiomas that were surgically removed at Weill Cornell Medical College between 2000 and 2015 (TCA) and 2008 and 2015 (EEA). All cases were shown to a panel of 3 neurosurgeons to find only those tumors that could be removed equally well either through an EEA or TCA to standardize both groups. Volumetric measurements of preoperative and postoperative tumor size, FLAIR images, and apparent diffusion coefficient maps were assessed by 2 independent reviewers and compared to assess extent of resection and trauma to the surrounding brain. Visual outcome and complications were also compared. RESULTS Thirty-two patients were identified who underwent either EEA (n = 17) or TCA (n = 15). The preoperative tumor size was comparable (mean 5.58 ± 3.42 vs 5.04 ± 3.38 cm [± SD], p = 0.661). The average extent of resection achieved was not significantly different between the 2 groups (98.80% ± 3.32% vs 95.13% ± 11.69%, p = 0.206). Postoperatively, the TCA group demonstrated a significant increase in the FLAIR/edema signal compared with EEA patients (4.15 ± 7.10 vs -0.69 ± 2.73 cm, p = 0.014). In addition, the postoperative diffusion-weighted imaging signal of cytotoxic ischemic damage was significantly higher in the TCA group than in the EEA group (1.88 ± 1.96 vs 0.40 ± 0.55 cm, p =0.008). Overall, significantly more EEA patients experienced improved or stable visual outcomes compared with TCA patients (93% vs 56%, p = 0.049). Visual deterioration was greater after TCA than EEA (44% vs 0%, p = 0.012). While more patients experienced postoperative seizures after TCA than after EEA (27% vs 0%, p = 0.038), there was a trend toward more CSF leakage and anosmia after EEA than after TCA (11.8% vs 0%, p = 0.486 and 11.8% vs 0%, p = 0.118, respectively). CONCLUSIONS In this small single-institution study of similarly sized and located PS and TS meningiomas, EEA provided equivalent rates of resection with better visual results, less trauma to the brain, and fewer seizures. These preliminary results merit further investigation in a larger multiinstitutional study and may support EEA resection by experienced surgeons in a subset of carefully selected PS and TS meningiomas.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2025 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.