Characterisation of LGP2 complex multitranscript system in humans: role in the innate immune response and evolution from non-human primates.

Retinoic acid inducible gene I (RIG-I)-like receptors (RLRs), including RIG-I, MDA5 and LGP2, recognize viral RNA to mount an antiviral interferon (IFN) response RLRs share three different protein domains: C-terminal domain, DExD/H box RNA helicase domain, and an N-terminal domain with two tandem repeats (CARDs). LGP2 lacks tandem CARD and is not able to induce an IFN response. However, LGP2 positively enhances MDA5 and negatively regulates RIG-I signaling.

Pre-existing cell populations with cytotoxic activity against SARS-CoV-2 in people with HIV and normal CD4/CD8 ratio previously unexposed to the virus.

Introduction: HIV-1 infection may produce a detrimental effect on the immune response. Early start of antiretroviral therapy (ART) is recommended to preserve the integrity of the immune system. In fact, people with HIV (PWH) and normal CD4/CD8 ratio appear not to be more susceptible to severe forms of COVID-19 than the general population and they usually present a good seroconversion rate in response to vaccination against SARS-CoV-2.

Sustained Cytotoxic Response of Peripheral Blood Mononuclear Cells from Unvaccinated Individuals Admitted to the ICU Due to Critical COVID-19 Is Essential to Avoid a Fatal Outcome.

The main objective of this study was to determine the influence of the cytotoxic activity of peripheral blood mononuclear cells (PBMCs) on the outcome of unvaccinated individuals with critical COVID-19 admitted to the ICU. Blood samples from 23 individuals were collected upon admission and then every 2 weeks for 13 weeks until death (Exitus group) ( = 13) or discharge (Survival group) ( = 10). We did not find significant differences between groups in sociodemographic, clinical, or biochemical data that may influence the fatal outcome.

Cytokine Deficiencies in Patients with Long-COVID.

Up to half of individuals who contract SARS-CoV-2 develop symptoms of long-COVID approximately three months after initial infection. These symptoms are highly variable, and the mechanisms inducing them are yet to be understood. We compared plasma cytokine levels from individuals with long-COVID to healthy individuals and found that those with long-COVID had 100% reductions in circulating levels of Interferon Gamma (IFNγ) and Interleukin-8 (IL-8).

Dasatinib: effects on the macrophage phospho proteome with a focus on SAMHD1 and HIV-1 infection.

Macrophages are one of the main cellular targets of human immunodeficiency virus type 1 (HIV-1). Macrophage infection by HIV-1 is inefficient due to the presence of the viral restriction factor sterile alpha motif and histidine aspartic acid domain containing protein 1 (SAMHD1). human monocyte-derived macrophages (MDMs) express SAMHD1 in an equilibrium between active (unphosphorylated) and inactive (phosphorylated) states.

Strong Humoral but Not Cellular Immune Responses against SARS-CoV-2 in Individuals with Oncohematological Disease Who Were Treated with Rituximab before Receiving a Vaccine Booster.

The humoral immune response developed after receiving the full vaccination schedule against COVID-19 is impaired in individuals who received anti-CD20 therapy 6-9 months before vaccination. However, there is little information about the cellular immune responses elicited in these individuals. In this study, we analyzed the humoral and cellular immune responses in 18 individuals with hematological disease who received the last dose of rituximab 13.

Plasma cytokine levels reveal deficiencies in IL-8 and gamma interferon in Long-COVID.

Up to half of individuals who contract SARS-CoV-2 develop symptoms of long-COVID approximately three months after initial infection. These symptoms are highly variable, and the mechanisms inducing them are yet to be understood. We compared plasma cytokine levels from individuals with long-COVID to healthy individuals and found that those with long-COVID had 100% reductions in circulating levels of interferon gamma (IFNγ) and interleukin-8 (IL-8).

Association between HLA-C alleles and COVID-19 severity in a pilot study with a Spanish Mediterranean Caucasian cohort.

The clinical presentations of COVID-19 may range from an asymptomatic or mild infection to a critical or fatal disease. Several host factors such as elderly age, male gender, and previous comorbidities seem to be involved in the most severe outcomes, but also an impaired immune response that causes a hyperinflammatory state but is unable to clear the infection. In order to get further understanding about this impaired immune response, we aimed to determine the association of specific HLA alleles with different clinical presentations of COVID-19.

Beneficial Effect of Short-Term Supplementation of High Dose of Vitamin D in Hospitalized Patients With COVID-19: A Multicenter, Single-Blinded, Prospective Randomized Pilot Clinical Trial.

There is now sufficient evidence to support that vitamin D deficiency may predispose to SARS-CoV-2 infection and increase COVID-19 severity and mortality. It has been suggested that vitamin D supplementation may be used prophylactically as an affordable and safe strategy that could be added to the existing COVID-19 standard treatment. This multicenter, single-blinded, prospective randomized pilot clinical trial aimed to evaluate the safety, tolerability, and effectiveness of 10,000 IU/day in comparison with 2000 IU/day of cholecalciferol supplementation for 14 days to reduce the duration and severity of COVID-19 in 85 hospitalized individuals.

Dynamics of HIV Reservoir and HIV-1 Viral Splicing in HCV-Exposed Individuals after Elimination with DAAs or Spontaneous Clearance.

Background: Although human immunodeficiency virus type 1 (HIV-1) reservoir size is very stable under antiretroviral therapy (ART), individuals exposed to the Hepatitis C virus (HCV) (chronically coinfected and spontaneous clarifiers) show an increase in HIV reservoir size and in spliced viral RNA, which could indicate that the viral protein regulator Tat is being more actively synthesized and, thus, could lead to a higher yield of new HIV. However, it is still unknown whether the effect of HCV elimination with direct-acting antivirals (DAAs) could modify the HIV reservoir and splicing. Methods: This longitudinal study (48 weeks’ follow-up after sustained virological response) involves 22 HIV+-monoinfected individuals, 17 HIV+/HCV- spontaneous clarifiers, and 24 HIV+/HCV+ chronically infected subjects who eliminated HCV with DAAs (all of them aviremic, viral load < 50).

Transcriptomic Evidence of the Immune Response Activation in Individuals With Limb Girdle Muscular Dystrophy Dominant 2 (LGMDD2) Contributes to Resistance to HIV-1 Infection.

LGMDD2 is a rare form of muscular dystrophy characterized by one of the three heterozygous deletions described within the gene that result in the addition of a 15-amino acid tail in the C-terminus.TNPO3 is involved in the nuclear import of splicing factors and acts as a host cofactor for HIV-1 infection by mechanisms not yet deciphered. Further characterization of the crosstalk between HIV-1 infection and LGMDD2 disease may contribute to a better understanding of both the cellular alterations occurring in LGMDD2 patients and the role of TNPO3 in the HIV-1 cycle.

Early Cellular and Humoral Responses Developed in Oncohematological Patients after Vaccination with One Dose against COVID-19.

Individuals with oncohematological diseases (OHD) may develop an impaired immune response against vaccines due to the characteristics of the disease or to its treatment. Humoral response against SARS-CoV-2 has been described to be suboptimal in these patients, but the quality and efficiency of the cellular immune response has not been yet completely characterized. In this study, we analyzed the early humoral and cellular immune responses in individuals with different OHD after receiving one dose of an authorized vaccine against SARS-CoV-2.

Changes in the immune response against SARS-CoV-2 in individuals with severe COVID-19 treated with high dose of vitamin D.

Main cause of severe illness and death in COVID-19 patients appears to be an excessive but ineffectual inflammatory immune response that may cause severe acute respiratory distress syndrome (ARDS). Vitamin D may favour an anti-inflammatory environment and improve cytotoxic response against some infectious diseases. A multicenter, single-blind, prospective, randomized clinical trial was approved in patients with COVID-19 pneumonia and levels of 25-hydroxyvitamin D (25(OH)D) of 14.

Strong Cellular Immune Response, but Not Humoral, against SARS-CoV-2 in Oncohematological Patients with Autologous Stem Cell Transplantation after Natural Infection.

Oncohematological patients show a low immune response against SARS-CoV-2, both to natural infection and after vaccination. Most studies are focused on the analysis of the humoral response; therefore, the information available about the cellular immune response is limited. In this study, we analyzed the humoral and cellular immune responses in nine individuals who received chemotherapy for their oncohematological diseases, as well as consolidation with autologous stem cell transplantation (ASCT), after being naturally infected with SARS-CoV-2.

HIV-1 Accessory Proteins Impart a Modest Interferon Response and Upregulate Cell Cycle-Related Genes in Macrophages.

HIV-1 infection of myeloid cells is associated with the induction of an IFN response. How HIV-1 manipulates and subverts the IFN response is of key interest for the design of therapeutics to improve immune function and mitigate immune dysregulation in people living with HIV. HIV-1 accessory genes function to improve viral fitness by altering host pathways in ways that enable transmission to occur without interference from the immune response.

Impaired Antibody-Dependent Cellular Cytotoxicity in a Spanish Cohort of Patients With COVID-19 Admitted to the ICU.

SARS-CoV-2 infection causes COVID-19, ranging from mild to critical disease in symptomatic subjects. It is essential to better understand the immunologic responses occurring in patients with the most severe outcomes. In this study, parameters related to the humoral immune response elicited against SARS-CoV-2 were analysed in 61 patients with different presentations of COVID-19 who were recruited in Hospitals and Primary Healthcare Centres in Madrid, Spain, during the first pandemic peak between April and June 2020.