CD8-mediated virus inhibition can be detected in HIV-1-positive subjects who naturally control virus replication. Characterizing the inhibitory function of CD8(+) T cells during acute HIV-1 infection (AHI) can elucidate the nature of the CD8(+) responses that can be rapidly elicited and that contribute to virus control. We examined the timing and HIV-1 antigen specificity of antiviral CD8(+) T cells during AHI. Autologous and heterologous CD8(+) T cell antiviral functions were assessed longitudinally during AHI in five donors from the CHAVI 001 cohort using a CD8(+) T cell-mediated virus inhibition assay (CD8 VIA) and transmitted/founder (T/F) viruses. Potent CD8(+) antiviral responses against heterologous T/F viruses appeared during AHI at the first time point sampled in each of the 5 donors (Fiebig stages 1/2 to 5). Inhibition of an autologous T/F virus was durable to 48 weeks; however, inhibition of heterologous responses declined concurrent with the resolution of viremia. HIV-1 viruses from 6 months postinfection were more resistant to CD8(+)-mediated virus inhibition than cognate T/F viruses, demonstrating that the virus escapes early from CD8(+) T cell-mediated inhibition of virus replication. CD8(+) T cell antigen-specific subsets mediated inhibition of T/F virus replication via soluble components, and these soluble responses were stimulated by peptide pools that include epitopes that were shown to drive HIV-1 escape during AHI. These data provide insights into the mechanisms of CD8-mediated virus inhibition and suggest that functional analyses will be important for determining whether similar antigen-specific virus inhibition can be induced by T cell-directed vaccine strategies.
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http://dx.doi.org/10.1128/JVI.00437-12 | DOI Listing |
FASEB J
January 2025
National Key Laboratory of Space Medicine, China Astronaut Research and Training Center, Beijing, China.
Microgravity-induced cardiac remodeling and dysfunction present significant challenges to long-term spaceflight, highlighting the urgent need to elucidate the underlying molecular mechanisms and develop precise countermeasures. Previous studies have outlined the important role of miRNAs in cardiovascular disease progression, with miR-199a-3p playing a crucial role in myocardial injury repair and the maintenance of cardiac function. However, the specific role and expression pattern of miR-199a-3p in microgravity-induced cardiac remodeling remain unclear.
View Article and Find Full Text PDFNat Cancer
January 2025
Department of Cell Biology, Harvard Medical School, Boston, MA, USA.
Cancer cells frequently rewire their metabolism to support proliferation and evade immune surveillance, but little is known about metabolic targets that could increase immune surveillance. Here we show a specific means of mitochondrial respiratory complex I (CI) inhibition that improves tumor immunogenicity and sensitivity to immune checkpoint blockade (ICB). Targeted genetic deletion of either Ndufs4 or Ndufs6, but not other CI subunits, induces an immune-dependent growth attenuation in melanoma and breast cancer models.
View Article and Find Full Text PDFJ Dairy Sci
January 2025
Department of Animal Sciences, Center of Microbiome Science, The Ohio State University, Columbus, OH 43210.
The rumen microbiome is essential for breaking down indigestible plant material, supplying ruminants with most of their metabolizable energy and protein. While research has primarily focused on bacteria and archaea, protozoa and viruses (phages) have only gained attention in recent years. Protozoa contribute to feed digestion and fermentation, but as predators, they regulate microbial populations by lysing large quantities of microbial cells (the primary protein source for ruminants) and influence the amount of microbial protein reaching the small intestines, along with other mechanisms of interactions.
View Article and Find Full Text PDFToxicology
January 2025
Department of Pharmacology, Shantou University Medical College, Shantou 515041, China. Electronic address:
Aflatoxin B1 (AFB1) has been reported to synergize with hepatitis B virus (HBV) to induce development of hepatocellular carcinoma (HCC). Precise daily exposure to AFB1 and its contribution to liver injury have not been quantified and have even been disregarded due to lack of convenient detection, and the strong species specificity of HBV infection has restricted research on their synergistic harm. Hence, our objective was to investigate the molecular mechanisms by which AFB1 exacerbates HBV-related injury.
View Article and Find Full Text PDFSLAS Discov
January 2025
Center for Discovery and Innovation, Hackensack Meridian Health, 111 Ideation Way. Nutley, New Jersey 07110, United States. Electronic address:
The COVID-19 pandemic has emphasized the necessity for rapid and adaptable drug screening platforms against live pathogenic viruses that require high levels of biosafety containment. Conventional antiviral testing is time-consuming and labor-intensive. Here, we outline the design and validation of a semi-automated drug-screening platform for SARS-CoV-2 that utilizes multiple liquid handlers, a stable A549 cell line expressing ACE2 and TMPRSS2 receptors, and a recombinant SARS-CoV-2 strain harboring the nano-luciferase gene.
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