Scroll through the 6 publications from CERID labs, PIs, and lab technicians publications that have hit the PubMed stands since the end of July! The scope of the publications is wide, covering a number of important pathogens and viruses from SARS-CoV-2 infection to Zika virus. Read on for highlights from the abstract and the diseases studied in this month’s publication roundup by following the links! Publications are listed by the date published. All descriptions of the work have been paraphrased from the publications' respective abstracts and are cited as such.
Zika virus (ZIKV) is a mosquito-borne pathogen that caused an epidemic in 2015-2016. ZIKV-specific T cell responses are functional in animal infection models, and helper CD4 T cells promote avid Abs in the vaccine context. The small volumes of blood available from field research limit the determination of T cell epitopes for complex microbes such as ZIKV. The goal of this project was efficient determination of human ZIKV CD4 T cell epitopes at the whole proteome scale, including validation of reactivity to whole pathogen, using small blood samples from convalescent time points when T cell response magnitude may have waned. Polyclonal enrichment of candidate ZIKV-specific CD4 T cells used cell-associated virus, documenting that T cells in downstream peptide analyses also recognize whole virus after Ag processing. Sequential query of bulk ZIKV-reactive CD4 T cells with pooled/single ZIKV peptides and molecularly defined APC allowed precision epitope and HLA restriction assignments across the ZIKV proteome and enabled discovery of numerous novel ZIKV CD4 T cell epitopes. The research workflow is useful for the study of emerging infectious diseases with a very limited human blood sample availability. Read the full article here!
Blood disorders, diseases, and infections often affect the shape, number, and content of red blood cells (RBCs) dramatically. To combat these pathologies, many therapies target RBCs and their contents directly. Mean corpuscular hemoglobin concentration (MCHC) is an important pathological metric in both identification and treatment. However, current methods for RBC analysis and MCHC quantification rely on bulk measurements. Single RBC measurements could provide necessary insight into the heterogeneity of RBC health and improve therapeutic efficacy. In this study, we present a novel multimodal multiphoton approach for quantifying hemoglobin concentration at single RBC resolution. We achieve this by collecting two images simultaneously that allows us to excite water with stimulated Raman scattering and hemoglobin with transient absorption. This multimodal imaging is enabled by a newly designed orthogonal modulation theme for dual-channel lock-in detection. By leveraging water as an internal standard, we quantify MCHC of healthy RBCs and RBCs infected with Plasmodium yoelii, a commonly studied rodent parasite model. Read the full article here!
The essential scope of the coronavirus infectious disease 2019 (COVID-19) pandemic is focused on developing effective treatments and vaccines for acute SARS-CoV-2 infection. There is also a critical need to develop interventions to prevent the complications of COVID-19, which occur with an alarming frequency in older adults. Since severe pathologic effects of infection occur with increasing age, COVID-19 falls under the geroscience concept that all diseases in older adults have a common and major underlying cause of declining function and resilience. Geroscience posits that manipulation of aging will simultaneously delay the appearance or severity of major diseases because they share the same risk factor: aging and the multiple processes involved in aging. Drug combinations that target multiple aging processes and the cytokine networks associated with them would not necessarily limit SARS-CoV-2 infection rates but would prevent severe pathologic consequences of the disease in older adults by maintaining a more youthful-like resilience to infection-related complications. A drug cocktail aimed at controlling cytokine actions would complement current clinical treatments and vaccine effectiveness for COVID-19 and serve as a prototype for future age-related infectious disease pandemics wherein the elderly population is especially vulnerable. Read the full article here!
Influenza A viruses (IAVs) remain a significant global health burden. Activation of the innate immune response is important for controlling early virus replication and spread. It is unclear how early IAV replication events contribute to immune detection. Additionally, while many cell types in the lung can be infected, it is not known if all cell types contribute equally to establish the antiviral state in the host. Here, we use single-cycle influenza A viruses (scIAVs) to characterize the early immune response to IAV in vitro and in vivo. We found that the magnitude of virus replication contributes to antiviral gene expression within infected cells prior to the induction of a global response. We also developed a scIAV that is only capable of undergoing primary transcription, the earliest stage of virus replication. Using this tool, we uncovered replication stage-specific responses in vitro and in vivo. Using several innate immune receptor knockout cell lines, we identify RIG-I as the predominant antiviral detector of primary virus transcription and amplified replication in vitro. Through a Cre-inducible reporter mouse, we used scIAVs expressing Cre-recombinase to characterize cell type-specific responses in vivo. Individual cell types upregulate unique sets of antiviral genes in response to both primary virus transcription and amplified replication. We also identified antiviral genes that are only upregulated in response to direct infection. Altogether, these data offer insight into the early mechanisms of antiviral gene activation during influenza A infection. Read the full article here!
The Senegal pre-exposure prophylaxis (PrEP) Demonstration Project was an open-label cohort study assessing the delivery of daily oral PrEP to HIV-negative female sex workers (FSWs) in four Ministry of Health (MoH)-run clinics in Dakar, Senegal. We assessed uptake, retention in care, and adherence over up to 12 months of follow-up as well as HIV infection rates. Between July and November 2015, 350 individuals were approached and 324 (92.6%) were preliminarily eligible. Uptake was high, with 82.4% of eligible participants choosing to enroll and take PrEP. The mean age of those enrolled was 37.7 years (SD = 8.7), and approximately half had not attended school (41.2%). Among the 267 participants who were prescribed PrEP, 79.9 and 73.4% were retained in PrEP care at 6 and 12 months, respectively. Older age among FSWs was found to be the only significant predictor of lower discontinuation. We did not find significant differences in retention by site, education, condom use, or HIV risk perception. There were no new HIV infections at follow-up. Our results showed evidence of high interest in PrEP and very good PrEP retention rates among FSWs at 12-month follow-up when offered in MoH-run clinics, with older age as the only significant predictor of higher PrEP retention. This highlights the role that these clinics can play in expanding PrEP access nationwide. Read the full article here!
A 53-year-old woman presented with progressive headache and gait instability. MRI showed an enhancing intraaxial lesion (2.0 cm by 1.8 cm by 1.7 cm) in the right cerebellar hemisphere. An HIV screening assay was reactive, but plasma HIV-1 RNA was not detected; the CD4+ T-cell count was 39 per microliter. Diagnostic tests were performed. Read the full case here!