SARS-CoV-2 ORF8 drives osteoclastogenesis in preexisting immune-mediated inflammatory diseases.

Patients with immune-mediated inflammatory diseases (IMIDs) like rheumatoid arthritis (RA) are at higher risk for severe COVID-19 and long-term complications in bone health. Emerging clinical evidence demonstrated that SARS-CoV-2 infection reduces bone turnover and promotes bone loss, but the mechanism underlying worsened bone health remains elusive. This study sought to identify specific immune mediators that exacerbated preexisting IMIDs after SARS-CoV-2 exposure.

Transplacental SARS-CoV-2 protein ORF8 binds to complement C1q to trigger fetal inflammation.

Prenatal SARS-CoV-2 infection is associated with higher rates of pregnancy and birth complications, despite that vertical transmission rates are thought to be low. Here, multi-omics analyses of human placental tissues, cord tissues/plasma, and amniotic fluid from 23 COVID-19 mother-infant pairs revealed robust inflammatory responses in both maternal and fetal compartments. Pronounced expression of complement proteins (C1q, C3, C3b, C4, C5) and inflammatory cytokines (TNF, IL-1α, and IL-17A/E) was detected in the fetal compartment of COVID-19-affected pregnancies.

Sustained chronic inflammation and altered childhood vaccine responses in children exposed to Zika virus.

Background: Congenital Zika virus (ZIKV) infection leads to severe newborn abnormalities, but its long-term impact on childhood immunity is not well understood. This study aims to investigate the serum proteomics in children exposed to ZIKV during pregnancy to understand potential immunological consequences during early childhood.

Methods: The study included ZIKV-exposed infants (ZEI) at birth (n = 42) and children exposed to ZIKV (ZEC) at two years of age (n = 20) exposed to ZIKV during pregnancy, as well as healthy controls.

TXNIP-mediated crosstalk between oxidative stress and glucose metabolism.

Thioredoxin-interacting protein (TXNIP) has emerged as a key player in cancer and diabetes since it targets thioredoxin (TRX)-mediated redox regulation and glucose transporter (GLUT)-mediated metabolism. TXNIP consists of two arrestin (ARR, N-ARR and C-ARR) domains at its amino-terminus and two PPxY (PY) motifs and a di-leucine (LL) motif for endocytosis at its carboxyl-terminus. Here, we report that TXNIP shuffles between TRX and GLUTs to regulate homeostasis of intracellular oxidative stress and glucose metabolism.

Mechanistic insights into bone remodelling dysregulation by human viral pathogens.

Bone-related diseases (osteopathologies) associated with human virus infections have increased around the globe. Recent findings have highlighted the intricate interplay between viral infection, the host immune system and the bone remodelling process. Viral infections can disrupt bone homeostasis, contributing to conditions such as arthritis and soft tissue calcifications.

Respiratory distress in SARS-CoV-2 exposed uninfected neonates followed in the COVID Outcomes in Mother-Infant Pairs (COMP) Study.

Respiratory distress (RD) has been reported in SARS-CoV-2 exposed uninfected (SEU) term neonates. Prior studies suggest that prenatal exposure to Coronavirus Disease 19 (COVID-19) may activate an inflammatory cascade in the newborn airway. In this study, we examine the relationship between maternal COVID-19 vaccination and neonatal RD using a longitudinal cohort of mother-infant pairs in Los Angeles, CA.

Immunometabolic rewiring in long COVID patients with chronic headache.

Almost 20% of patients with COVID-19 experience long-term effects, known as post-COVID condition or long COVID. Among many lingering neurologic symptoms, chronic headache is the most common. Despite this health concern, the etiology of long COVID headache is still not well characterized.

Neuromotor repertoires in infants exposed to maternal COVID-19 during pregnancy: a cohort study.

Objective: To evaluate neuromotor repertoires and developmental milestones in infants exposed to antenatal COVID-19.

Design: Longitudinal cohort study.

Setting: Hospital-based study in Los Angeles, USA and Rio de Janeiro, Brazil between March 2020 and December 2021.

OASL phase condensation induces amyloid-like fibrillation of RIPK3 to promote virus-induced necroptosis.

RIPK3-ZBP1-MLKL-mediated necroptosis is a proinflammatory cell death process that is crucial for antiviral host defence. RIPK3 self-oligomerization and autophosphorylation are prerequisites for executing necroptosis, yet the underlying mechanism of virus-induced RIPK3 activation remains elusive. Interferon-inducible 2'-5' oligoadenylate synthetase-like (OASL) protein is devoid of enzymatic function but displays potent antiviral activity.

Longitudinal Evaluation of Antibody Persistence in Mother-Infant Dyads After Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Pregnancy.

Background: There are limited data on how coronavirus disease 2019 (COVID-19) severity, timing of infection, and subsequent vaccination impact transplacental transfer and persistence of maternal and infant antibodies.

Methods: In a longitudinal cohort of pregnant women with polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, maternal/infant sera were collected at enrollment, delivery/birth, and 6 months. Anti-SARS-CoV-2 spike immunoglobulin (Ig)G, IgM, and IgA were measured by enzyme-linked immunosorbent assay.

Single-cell analysis of Kaposi's sarcoma-associated herpesvirus infection in three-dimensional air-liquid interface culture model.

The oral cavity is the major site for transmission of Kaposi's sarcoma-associated herpesvirus (KSHV), but how KSHV establishes infection and replication in the oral epithelia remains unclear. Here, we report a KSHV spontaneous lytic replication model using fully differentiated, three-dimensional (3D) oral epithelial organoids at an air-liquid interface (ALI). This model revealed that KSHV infected the oral epithelia when the basal epithelial cells were exposed by damage.

Viral Mimicry of Interleukin-17A by SARS-CoV-2 ORF8.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection triggers cytokine-mediated inflammation, leading to a myriad of clinical presentations in COVID-19. The SARS-CoV-2 open reading frame 8 (ORF8) is a secreted and rapidly evolving glycoprotein. Patients infected with SARS-CoV-2 variants with ORF8 deleted are associated with mild disease outcomes, but the molecular mechanism behind this is unknown.

The systemic inflammatory landscape of COVID-19 in pregnancy: Extensive serum proteomic profiling of mother-infant dyads with SARS-CoV-2.

While pregnancy increases the risk for severe COVID-19, the clinical and immunological implications of COVID-19 on maternal-fetal health remain unknown. Here, we present the clinical and immunological landscapes of 93 COVID-19 mothers and 45 of their SARS-CoV-2-exposed infants through comprehensive serum proteomics profiling for >1,400 cytokines of their peripheral and cord blood specimens. Prenatal SARS-CoV-2 infection triggers NF-κB-dependent proinflammatory immune activation.

Molecular Signatures of Inflammatory Profile and B-Cell Function in Patients with Severe Fever with Thrombocytopenia Syndrome.

Dabie bandavirus (severe fever with thrombocytopenia syndrome virus [SFTSV]) induces an immunopathogenic disease with a high fatality rate; however, the mechanisms underlying its clinical manifestations are largely unknown. In this study, we applied targeted proteomics and single-cell transcriptomics to examine the differential immune landscape in SFTS patient blood. Serum immunoprofiling identified low-risk and high-risk clusters of SFTS patients based on inflammatory cytokine levels, which corresponded to disease severity.

Zika virus NS3 protease induces bone morphogenetic protein-dependent brain calcification in human fetuses.

The most frequent fetal birth defect associated with prenatal Zika virus (ZIKV) infection is brain calcification, which in turn may potentially affect neurological development in infants. Understanding the mechanism could inform the development of potential therapies against prenatal ZIKV brain calcification. In perivascular cells, bone morphogenetic protein (BMP) is an osteogenic factor that undergoes maturation to activate osteogenesis and calcification.

Zika virus vertical transmission in children with confirmed antenatal exposure.

We report Zika virus (ZIKV) vertical transmission in 130 infants born to PCR+ mothers at the time of the Rio de Janeiro epidemic of 2015-2016. Serum and urine collected from birth through the first year of life were tested by quantitative reverse transcriptase polymerase chain reaction (PCR) and/or IgM Zika MAC-ELISA. Four hundred and seven specimens are evaluated; 161 sera tested by PCR and IgM assays, 85 urines by PCR.

Infection and Rapid Transmission of SARS-CoV-2 in Ferrets.

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China and rapidly spread worldwide. To prevent SARS-CoV-2 dissemination, understanding the in vivo characteristics of SARS-CoV-2 is a high priority. We report a ferret model of SARS-CoV-2 infection and transmission that recapitulates aspects of human disease.

Modulation of Monocyte-Driven Myositis in Alphavirus Infection Reveals a Role for CXCR1 Macrophages in Tissue Repair.

Arthritogenic alphaviruses such as Ross River and Chikungunya viruses cause debilitating muscle and joint pain and pose significant challenges in the light of recent outbreaks. How host immune responses are orchestrated after alphaviral infections and lead to musculoskeletal inflammation remains poorly understood. Here, we show that myositis induced by Ross River virus (RRV) infection is driven by CD11b Ly6C inflammatory monocytes and followed by the establishment of a CD11b Ly6C CXCR1 macrophage population in the muscle upon recovery.

Efficient Inhibition of Human Papillomavirus Infection by L2 Minor Capsid-Derived Lipopeptide.

The amino (N)-terminal region of human papillomavirus (HPV) minor capsid protein (L2) is a highly conserved region which is essential for establishing viral infection. Despite its importance in viral infectivity, the role of the HPV N-terminal domain has yet to be fully characterized. Using fine mapping analysis, we identified a 36-amino-acid (aa) peptide sequence of the L2 N terminus, termed L2N, that is critical for HPV infection.

Association Between Neonatal Neuroimaging and Clinical Outcomes in Zika-Exposed Infants From Rio de Janeiro, Brazil.

Importance: Congenital Zika virus (ZIKV) infection may present with a spectrum of clinical and neuroradiographic findings.

Objective: To determine whether neuroimaging findings for infants with a history of ZIKV exposure are associated with infant clinical outcomes and gestational age at antenatal ZIKV infection.

Design, Setting, And Participants: This cohort study retrospectively reviewed neuroimaging results (computed tomography and/or magnetic resonance imaging scans) of 110 ZIKV-exposed infants from a maternity and children's hospital in Rio de Janeiro, Brazil, following the 2015 to 2016 ZIKV epidemic.

Severe fever with thrombocytopenia syndrome phlebovirus non-structural protein activates TPL2 signalling pathway for viral immunopathogenesis.

Severe fever with thrombocytopenia syndrome phlebovirus (SFTSV), listed in the World Health Organization Prioritized Pathogens, is an emerging phlebovirus with a high fatality. Owing to the lack of therapies and vaccines, there is a pressing need to understand SFTSV pathogenesis. SFSTV non-structural protein (NSs) has been shown to block type I interferon induction and facilitate disease progression.

Biomarkers and immunoprofiles associated with fetal abnormalities of ZIKV-positive pregnancies.

Background: An intricate fetal-maternal immune crosstalk during pregnancy is essential for a healthy birth. Hence, the infection-induced alterations of maternal immunity often lead to adverse outcomes for mother and/or child. The emergence of Zika virus (ZIKV) infection in pregnant women has been associated with more than 3,000 cases of microcephaly and nervous system malformations.

Specific inhibition of NLRP3 in chikungunya disease reveals a role for inflammasomes in alphavirus-induced inflammation.

Mosquito-borne viruses can cause severe inflammatory diseases and there are limited therapeutic solutions targeted specifically at virus-induced inflammation. Chikungunya virus (CHIKV), a re-emerging alphavirus responsible for several outbreaks worldwide in the past decade, causes debilitating joint inflammation and severe pain. Here, we show that CHIKV infection activates the NLRP3 inflammasome in humans and mice.

Asian Zika virus strains target CD14 blood monocytes and induce M2-skewed immunosuppression during pregnancy.

Blood CD14 monocytes are frontline immunomodulators categorized into classical, intermediate or non-classical subsets, and subsequently differentiated into M1 pro- or M2 anti-inflammatory macrophages on stimulation. Although the Zika virus (ZIKV) rapidly establishes viraemia, the target cells and immune responses, particularly during pregnancy, remain elusive. Furthermore, it is unknown whether African- and Asian-lineage ZIKV have different phenotypic impacts on host immune responses.