The HUSH epigenetic repressor complex silences PML nuclear body-associated HSV-1 quiescent genomes.

Herpes simplex virus 1 (HSV-1) latently infected neurons display diverse patterns in the distribution of the viral genomes within the nucleus. A key pattern involves quiescent HSV-1 genomes sequestered in promyelocytic leukemia nuclear bodies (PML NBs) forming viral DNA-containing PML-NBs (vDCP NBs). Using a cellular model that replicates vDCP NB formation, we previously demonstrated that these viral genomes are chromatinized with the H3.

Identification of macaque dendritic cell precursors in blood and tissue reveals their dysregulation in early SIV infection.

Distinct dendritic cell (DC) subsets play important roles in shaping immune responses. Circulating DC precursors (pre-DCs) are more susceptible to HIV infection in vitro, which may explain the inefficiency of immune responses against HIV. However, the interplay between HIV and pre-DC is not defined in vivo.

Integrative temporal multi-omics reveals uncoupling of transcriptome and proteome during human T cell activation.

Engagement of the T cell receptor (TCR) triggers molecular reprogramming leading to the acquisition of specialized effector functions by CD4 helper and CD8 cytotoxic T cells. While transcription factors, chemokines, and cytokines are known drivers in this process, the temporal proteomic and transcriptomic changes that regulate different stages of human primary T cell activation remain to be elucidated. Here, we report an integrative temporal proteomic and transcriptomic analysis of primary human CD4 and CD8 T cells following ex vivo stimulation with anti-CD3/CD28 beads, which revealed major transcriptome-proteome uncoupling.

Ocular surface toxicities associated with modern anticancer therapies.

Cancer treatments have recently shifted from broad-spectrum cytotoxic therapies to more focused treatments, maximizing anticancerous activity while reducing toxicity to healthy cells. These modern anticancer therapies (MATs) encompass a wide range of innovative molecules that include immune checkpoint inhibitors and other targeted anticancer therapies, comprising antibody drug conjugates and inhibitors of signal transduction. Some MATs are associated with ocular surface adverse events that can cause severe discomfort and even lead to loss of vision.

[Monkeypox: Important facts for the ophthalmologist].

The current monkeypox virus (MPXV) outbreak, raging since May 2022, is the largest ever observed on a world-wide scale. Despite previously being endemic in west and central Africa with a mortality rate of up to 10%, it remained a neglected tropical disease. Along with other recent pandemics gaining much attention, this MPXV outbreak has provided an opportunity to improve our understanding of its physiopathology and better define management strategies, particularly in patients with more serious disease.

Conjunctival conveyance of SARS-CoV-2 in asymptomatic and non-severe symptomatic COVID-19 patients.

Introduction: The prevalence of ocular conveyance of SARS-CoV-2 has been well described for severe/hospitalized cases, but scarcely reported in asymptomatic and non-severe patients, who are unaware that they are carriers.

Material & Methods: This prospective cross-sectional study quantitatively evaluated SARS-CoV-2 shedding on the ocular surface (OS). Conjunctival testing was suggested to all hospital personnel being screened by nasopharyngeal (NP) SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR).

Associations between ocular and extra-ocular assessment in primary Sjögren's syndrome.

Objectives: To assess associations between ophthalmological features and the main systemic biomarkers of primary Sjögren's Syndrome (pSS), and to identify systemic biomarkers associated with severe keratoconjunctivitis sicca (KCS) in pSS patients.

Methods: In this cross-sectional study, data was retrospectively extracted from the monocentric cohort of the French reference centre for pSS. We analysed data from the initial visit of patients admitted for suspicion of pSS and included patients validating pSS ACR/EULAR classification criteria.

Initial TK-deficient HSV-1 infection in the lip alters contralateral lip challenge immune dynamics.

Primary infection with herpes simplex type 1 (HSV-1) occurring around the mouth and nose switches rapidly to lifelong latent infection in sensitive trigeminal ganglia (TG) neurons. Sporadic reactivation of these latent reservoirs later in life is the cause of acute infections of the corneal epithelium, which can cause potentially blinding herpes simplex keratitis (HSK). There is no effective vaccine to protect against HSK, and antiviral drugs provide only partial protection against recurrences.

Rubella virus-associated uveitis: The essentiality of aqueous humor virological analysis.

Aims / Background: Rubella virus-associated uveitis (RVAU) classically presents with the clinical features of Fuchs uveitis syndrome (FUS). We report a series RVAU, and discuss the relevance of available diagnostic strategies, and how vaccination could potentially prevent disease.

Methods: We retrospectively included patients with RV-positive aqueous humor (AH) with RT-PCR and/or intraocular RV-IgG production, between January 2014 and December 2019.

DROSHA but not DICER is required for human haematopoietic stem cell function.

Objectives: DROSHA and DICER have central roles in the biogenesis of microRNAs (miRNAs). However, we previously showed that in the murine system, DROSHA has an alternate function where it directly recognises and cleaves protein-coding messenger (m)RNAs and this is critical for safeguarding the pluripotency of haematopoietic stem cells (HSCs). Maintenance of murine HSC function is dependent on DROSHA-mediated cleavage of two mRNAs, and .

Herpes simplex virus, varicella-zoster virus and cytomegalovirus keratitis: Facts for the clinician.

Keratitis due to Herpes simplex virus (HSK), Varicella-Zoster virus (VZK) and Cytomegalovirus remains a frequent source of concern for many ophthalmologists. They are a frequent cause of emergency consultations at eye care centers and carry the risk of permanent loss of visual acuity or visual quality and/or chronic neurotrophic keratitis, resulting in a significant decrease in the quality of life. HSK and VZK can affect the corneal epithelium, stroma, or endothelium or a combination of layers.

Synthetic hookworm-derived peptides are potent modulators of primary human immune cell function that protect against experimental colitis in vivo.

The prevalence of autoimmune diseases is on the rise globally. Currently, autoimmunity presents in over 100 different forms and affects around 9% of the world's population. Current treatments available for autoimmune diseases are inadequate, expensive, and tend to focus on symptom management rather than cure.

Peripheral ulcerative keratitis in rheumatoid arthritis patients taking tocilizumab: paradoxical manifestation or insufficient efficacy?

Objectives: Peripheral ulcerative keratitis (PUK) is a severe corneal condition associated with uncontrolled RA. Tocilizumab (TCZ) is used to control RA, however, episodes of paradoxical ocular inflammation have been reported in TCZ-treated patients. We report a case series of PUK in TCZ-treated RA patients with ophthalmological and systemic findings and discuss the potential underlying mechanisms.

Using pre-existing social networks to determine the burden of disease and real-life needs in rare diseases: the example of Thygeson's superficial punctate keratitis.

Background: Thygeson's superficial punctate keratitis (TSPK) is a rare and still poorly understood disease of the ocular surface, responsible for recurrent episodes of photophobia and eye pain. While TSPK is considered as a benign condition, a subset of patients has frequent recurrences or even chronic disease, two situations in which there are currently no therapeutic guidelines. We used a preexisting Facebook TSPK patient support group to assess the clinical journey and the burden of disease of TSPK.

Ocular Manifestations of West Nile Virus.

Ocular manifestations are a feature of West Nile virus infection. They mostly occur in association with severe neuroinvasive disease. Linear chorioretinitis is suggestive of the diagnosis and may raise diagnostic suspicion when associated with evocative systemic signs, and in an epidemic context.

Human CLEC9A antibodies deliver NY-ESO-1 antigen to CD141 dendritic cells to activate naïve and memory NY-ESO-1-specific CD8 T cells.

Background: Dendritic cells (DCs) are crucial for the efficacy of cancer vaccines, but current vaccines do not harness the key cDC1 subtype required for effective CD8 T-cell-mediated tumor immune responses. Vaccine immunogenicity could be enhanced by specific delivery of immunogenic tumor antigens to CD141 DCs, the human cDC1 equivalent. CD141 DCs exclusively express the C-type-lectin-like receptor CLEC9A, which is important for the regulation of CD8 T cell responses.

Herpes Simplex Virus 1 Replication, Ocular Disease, and Reactivations from Latency Are Restricted Unilaterally after Inoculation of Virus into the Lip.

Ocular herpes simplex keratitis (HSK) is a consequence of viral reactivations from trigeminal ganglia (TG) and occurs almost exclusively in the same eye in humans. In our murine oro-ocular (OO) model, herpes simplex virus 1 (HSV-1) inoculation in one side of the lip propagates virus to infect the ipsilateral TG. Replication here allows infection of the brainstem and infection of the contralateral TG.