Roberto Bruzzone

HKU-Pasteur - The University of Hong Kong

Humans display substantial interindividual clinical variability after SARS-CoV-2 infection1–3, the genetic and immunological basis of which has begun to be deciphered⁴. However, the extent and drivers of population differences in immune responses to SARS-CoV-2 remain unclear. Here we report single-cell RNA-sequencing data for peripheral blood monon...

[This corrects the article DOI: 10.3389/fimmu.2021.761250.].

Gut microbes are associated with the development of depression based on extensive evidence. However, previous studies have led to conflicting reports on this association, posing challenges to the application of gut bacteria in the diagnostics and treatment of depression. To minimise heterogenicity in data analysis, the present meta-analysis adopted...

Background Four seasonal coronaviruses, including HCoV-229E and HCoV-OC43, HCoV-NL63 and HCoV-HKU1 cause approximately 15–30% of common colds in adults. However, the full landscape of the immune trajectory to these viruses that covers the whole childhood period are still not well understood. Methods We evaluated the serological responses against t...

Humans display vast clinical variability upon SARS-CoV-2 infection, partly due to genetic and immunological factors. However, the magnitude of population differences in immune responses to SARS-CoV-2 and the mechanisms underlying such variation remain unknown. Here we report single-cell RNA-sequencing data for peripheral blood mononuclear cells fro...

Egg-adaptive mutations in influenza hemagglutinin (HA) often emerge during the production of egg-based seasonal influenza vaccines, which contribute to the largest share in the global influenza vaccine market. While some egg-adaptive mutations have minimal impact on the HA antigenicity (e.g. G186V), others can alter it (e.g. L194P). Here, we show t...

Four seasonal coronaviruses, including NL63 and 229E, OC43 and HKU1 cause approximately 15-30% of common colds in adults. However, the frequency and timing of early infection with four seasonal coronaviruses in the infant are still not well studied. Here, we evaluated the serological response to four seasonal coronaviruses in 1886 children under 18...

Gut microbes are associated with the development of depression based on extensive evidence. However, previous studies have led to conflicting reports on this association, posing challenges to the application of the gut microbiota in the diagnostics and treatment of depression. To minimize heterogenicity in data analysis, the present meta-analysis a...

Egg-adaptive mutations in influenza hemagglutinin (HA) often emerge during the production of egg-based seasonal influenza vaccines, which contribute to the largest share in the global influenza vaccine market. While some egg-adaptive mutations have minimal impact on the HA antigenicity (e.g. G186V), others can alter it (e.g. L194P). Here, we show t...

Amino acid substitutions and deletions in the Spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants can reduce the effectiveness of monoclonal antibodies (mAbs). In contrast, heterologous polyclonal antibodies raised against S protein, through the recognition of multiple target epitopes, have the potential to mainta...

Heterologous polyclonal antibodies might represent an alternative to the use of convalescent plasma (CP) or monoclonal antibodies (mAbs) in COVID‐19 by targeting multiple antigen epitopes. However, heterologous antibodies trigger human natural xenogeneic antibody responses particularly directed against animal‐type carbohydrates, mainly the N‐glycol...

Among the various host cellular processes that are hijacked by flaviviruses, few mechanisms have been described with regard to viral egress. Here we investigate how flaviviruses exploit Src family kinases (SFKs) for exit from infected cells. We identify Lyn as a critical component for secretion of Dengue and Zika infectious particles and their corr...

Perfusion of convalescent plasma (CP) has demonstrated a potential to improve the pneumonia induced by SARS-CoV-2, but procurement and standardization of CP are barriers to its wide usage. Heterologous polyclonal antibodies of animal origin have been used to fight against infectious agents and are a possible alternative to the use of CP in SARS-CoV...

Interactions between the host and viruses during the course of their co-evolution have not only shaped cellular function and the immune system, but also the counter measures employed by viruses. Relatively small genomes and high replication rates allow viruses to accumulate mutations and continuously present the host with new challenges. It is ther...

Viral diseases remain serious threats to public health because of the shortage of effective means of control. To combat the surge of viral diseases, new treatments are urgently needed. Here we show that small-molecules, which inhibit cellular anti-apoptotic Bcl-2 proteins (Bcl-2i), induced the premature death of cells infected with different RNA or...

To identify new host factors that modulate the replication of influenza A virus, we performed a yeast two-hybrid screen using the cytoplasmic tail of matrix protein 2 from the highly pathogenic H5N1 strain. The screen revealed a high-score interaction with cyclin D3, a key regulator of cell cycle early G1 phase. M2-cyclin D3 interaction was validat...

Importance: Multiple pattern recognition receptors work in synergy to sense viral RNA or proteins synthesized during influenza replication and mediate host responses for viral control. Well-orchestrated host responses may help to maintain the inflammatory response at gate to minimize tissue damage while inducing an effective adaptive immune respon...

Significance We used an unbiased screening strategy to capture deubiquitylases that participate in T cell receptor signaling in primary cells under physiological settings. We identified ubiquitin-specific peptidase (Usp) 12 as a crucial component of TCR expression at the cell surface, and found supporting evidence for its function by creating an in...

Sensitization of the humoral immune response to invading viruses and production of antiviral antibodies forms part of the host antiviral repertoire. Paradoxically, for a number of viral pathogens, under certain conditions, antibodies provide an attractive means of enhanced virus entry and replication in a number of cell types. Known as antibody-dep...

The function of KDEL receptors (KDELR) is to capture endoplasmic reticulum (ER)-resident chaperones in the acidic environment of the Golgi apparatus, by recognizing their C-terminal motif, and retrieve them back to the ER [1]. Certain structural features of KDELR, for example a similar topology to that of G-protein-coupled receptors (GPCR), a large...

Although several genetic diseases are caused by mutations in channels made by connexin family members, there has been little progress in the development and validation of therapeutic options. An in vitro study in this issue of JID suggests that an anti-malarial drug may be beneficial in keratitis-ichthyosis deafness, a severe conexin channel diseas...

Membrane receptors at the surface of target cells are key host factors for virion entry; however, it is unknown whether trafficking and secretion of progeny virus requires host intracellular receptors. In this study, we demonstrate that dengue virus (DENV) interacts with KDEL receptors (KDELR), which cycle between the ER and Golgi apparatus, for ve...

Background Public health risks associated to infection by human coronaviruses remain considerable and vaccination is a key option for preventing the resurgence of severe acute respiratory syndrome coronavirus (SARS-CoV). We have previously reported that antibodies elicited by a SARS-CoV vaccine candidate based on recombinant, full-length SARS-CoV S...

Entry of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and its envelope fusion with host cell membrane are controlled by a series of complex molecular mechanisms, largely dependent on the viral envelope glycoprotein Spike (S). There are still many unknowns on the implication of cellular factors that regulate the entry process. We perform...

Ezrin accumulates at sites of entry of SARS-CoV S-pseudotyped lentiviral particles. Vero E6 cells stably expressing RFP-ezrinwt were seeded onto a microscopy culture dish and were inoculated with SARSpp harboring a GFP-tagged Vpr protein (SARSpp GFP-Vpr) on ice. Unbound particles were washed with cold medium. The culture dish was then placed in a 3...

Serological studies for influenza infection and vaccine response often involve microneutralization and hemagglutination inhibition assays to evaluate neutralizing antibodies against human and avian influenza viruses, including H5N1. We have previously characterized lentiviral particles pseudotyped with H5-HA (H5pp) and validated an H5pp-based assay...

1. A SARS vaccine was produced based on recombinant native full-length Spike-protein trimers (triSpike) and efficient establishment of a vaccination procedure in rodents. 2. Antibody-mediated enhancement of SARS-CoV infection with anti-SARS-CoV Spike immune-serum was observed in vitro. 3. Antibody-mediated infection of SARS-CoV triggers entry into...

Identification and characterization of virus-host interactions are very important steps toward a better understanding of the molecular mechanisms responsible for disease progression and pathogenesis. To date, very few cellular factors involved in the life cycle of flaviviruses, which are important human pathogens, have been described. In this study...

Public health measures successfully contained outbreaks of the severe acute respiratory syndrome coronavirus (SARS-CoV) infection. However, the precursor of the SARS-CoV remains in its natural bat reservoir, and reemergence of a human-adapted SARS-like coronavirus remains a plausible public health concern. Vaccination is a major strategy for contai...

Intercellular tight junctions define epithelial apicobasal polarity and form a physical fence which protects underlying tissues from pathogen invasions. PALS1, a tight junction-associated protein, is a member of the CRUMBS3-PALS1-PATJ polarity complex, which is crucial for the establishment and maintenance of epithelial polarity in mammals. Here we...

Coupling coefficients exhibited by fast-spiking interneurons in the neocortex*.

Connexin 36 (Cx36)-containing electrical synapses contribute to the timing and amplitude of neural responses in many brain regions. A Cx36-EGFP transgenic was previously generated to facilitate their identification and study. In this study we demonstrate that electrical coupling is normal in transgenic mice expressing Cx36 from the genomic locus an...

The four optimized DV prME sequences. Each optimized prME gene has a BamH I restriction enzyme site, a kozak sequence GCCACC, a signal sequences from VSV-G, and a Xho I restriction enzyme site. (0.03 MB DOC)

Flavivirus infected cells produce infectious virions and subviral particles, both of which are formed by the assembly of prM and E envelope proteins and are believed to undergo the same maturation process. Dengue recombinant subviral particles have been produced in cell cultures with either modified or chimeric proteins but not using the native for...

Entry of enveloped viruses into host cells requires the activation of viral envelope glycoproteins through cleavage by either intracellular or extracellular proteases. In order to gain insight into the molecular basis of protease cleavage and its impact on the efficiency of viral entry, we investigated the susceptibility of a recombinant native ful...

Two decades after its discovery the human immunodeficiency virus (HIV) is still spreading worldwide and killing millions. There are 25 drugs formally approved for HIV currently on the market, but side effects as well as the emergence of HIV strains showing single or multiple resistances to current drug-therapy are causes for concern. Furthermore, t...

The production of virus-like particles (VLPs) constitutes a relevant and safe model to study molecular determinants of virion egress. The minimal requirement for the assembly of VLPs for the coronavirus responsible for severe acute respiratory syndrome in humans (SARS-CoV) is still controversial. Recent studies have shown that SARS-CoV VLP formatio...

Antiviral immune defenses involve natural killer (NK) cells. We previously showed that the NK-activating receptor NKp44 is involved in the functional recognition of H1-type influenza virus strains by NK cells. In the present study, we investigated the interaction of NKp44 and the hemagglutinin of a primary influenza virus H5N1 isolate. Here we show...

Mammalian gap junction proteins, connexins, have long been implicated in tumor suppression. Recently, a novel family of proteins named pannexins has been identified as the mammalian counterpart of the invertebrate gap junction proteins, innexins. To date, pannexin 1 (Panx1) and pannexin 2 (Panx2) mRNAs are reported to be expressed in the brain. Mos...

Gap-junction-dependent neuronal communication is widespread in the developing brain, and the prevalence of gap-junctional coupling is well correlated with specific developmental events. We summarize here our current knowledge of the contribution of gap junctions to brain development and propose that they carry out this role by taking advantage of t...

Mutations in the GJB2 gene, which encodes the gap junction protein connexin26 (Cx26), are the major cause of genetic non-syndromic hearing loss. The role of the allelic variant M34T in causing hereditary deafness remains controversial. By combining genetic, clinical, biochemical, electrophysiological and structural modeling studies, we have re-asse...

Direct cell-to-cell communication through specialized intercellular channels is a characteristic feature of virtually all multi-cellular organisms. The remarkable functional conservation of cell-to-cell coupling throughout the animal kingdom, however, is not matched at the molecular level of the structural protein components. Thus protostomes (incl...

The X-linked form of Charcot-Marie-Tooth disease (CMTX) is caused by mutations in connexin32 (Cx32), a gap junction protein expressed by Schwann cells where it forms reflexive channels that allow the passage of ions and signaling molecules across the myelin sheath. Although most mutations result in loss of function, several studies have reported th...

Several new findings have emphasized the role of neuron-specific gap junction proteins (connexins) and electrical synapses in processing sensory information and in synchronizing the activity of neuronal networks. We have recently shown that pannexins constitute an additional family of proteins that can form gap junction channels in a heterologous e...

Genetic studies have conclusively linked connexin channels to human diseases, but the nature of the signals that are disrupted by channel mutations has remained elusive. A recent study has taken advantage of a deafness-causing mutation to suggest that permeability to inositol trisphosphate, the Ca2+-mobilizing messenger, is crucial for normal heari...

Clouston syndrome or hidrotic ectodermal dysplasia (HED) is a rare dominant genodermatosis characterized by palmoplantar hyperkeratosis, generalized alopecia and nail defects. The disease is caused by mutations in the human GJB6 gene which encodes the gap junction protein connexin30 (Cx30). To gain insight into the molecular mechanisms underlying H...

Gap junctions consist of intercellular channels dedicated to providing a direct pathway for ionic and biochemical communication between contacting cells. After an initial burst of publications describing electrical coupling in the brain, gap junctions progressively became less fashionable among neurobiologists, as the consensus was that this form o...

Gap junction-mediated electrical coupling contributes to synchronous oscillatory activities of neurons, and considerable progress has been made in defining the molecular composition of gap junction channels. In particular, cloning and functional expression of gap junction proteins (connexins (Cx)) from zebrafish retina have shown that this part of...