Related Experiment Video

Updated: Jul 12, 2026

Accessing Early Differentiation of Virus-Specific Follicular Helper CD4+ T Cell in Acute LCMV-Infected Mice
05:03

Accessing Early Differentiation of Virus-Specific Follicular Helper CD4+ T Cell in Acute LCMV-Infected Mice

Published on: April 26, 2024

Sp1 links CD46 to CD4 T cell metabolic fitness, survival, and retroviral control

Parul Singh1, Luopin Wang2, Pavitra Ramdas3

  • 1Complement and Inflammation Research Section, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD, USA.

Science Immunology
|July 10, 2026
PubMed

CD46, a human-specific complement receptor, regulates gene programs essential for T helper 1 (TH1) cell differentiation, yet how it exerts direct transcriptional control remains unclear. We show that the CD46 signaling domain cytoplasmic tail 1 (CYT-1) engages the transcription factor Sp1 in human CD4 T cells to dynamically modulate Sp1-DNA interactions. Beyond promoting TH1 cell induction, CD46-Sp1-controlled programs support naive CD4 T cell survival by maintaining nutrient transporter expression and suppressing the intrinsic caspase 9-caspase 3 apoptotic pathway. The CD46-Sp1 axis also restrains HIV transcription in infected CD4 T cells in vitro. Disruption of CYT-1-Sp1-regulated programs identifies T cells from individuals with HIV who exhibit incomplete viral suppression during antiretroviral therapy. Together, these findings define a human-specific transcriptional mechanism linking complement signaling to metabolic adaptation, apoptosis regulation, and antiviral defense, highlighting an unexpected role for CD46 in coordinating T cell homeostasis and host protection.

More Related Videos

Measuring Mitochondrial Function of Naïve and Effector CD8 T Cells06:07

Measuring Mitochondrial Function of Naïve and Effector CD8 T Cells

Published on: March 28, 2025

Retroviral Transduction of T-cell Receptors in Mouse T-cells10:14

Retroviral Transduction of T-cell Receptors in Mouse T-cells

Published on: October 22, 2010

Related Concept Videos

Mechanisms of Retrovirus-induced Cancers01:51

Mechanisms of Retrovirus-induced Cancers

Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
Mechanisms of Retrovirus-induced Cancers01:51

Mechanisms of Retrovirus-induced Cancers

Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
Retrovirus Life Cycles01:10

Retrovirus Life Cycles

Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the retrovirus to...
Retroviruses02:33

Retroviruses

Retroviruses and retrotransposons both insert copies of their genetic elements into the genome of the host cell. Thus, the viral genes are passed on when the host genome is replicated or translated. A typical retroviral DNA sequence contains 3-4 genes that encode the different proteins required for its structural assembly and function as a molecular parasite. This DNA is transcribed into a single mRNA, which is very similar in structure to conventional mRNAs, i.e., it is capped at the 5’...