In addition to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), humans are also susceptible to six other coronaviruses, for which consecutive exposures to antigenically related and ...divergent seasonal coronaviruses are frequent. Despite the prevalence of COVID-19 pandemic and ongoing research, the nature of the antibody response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. Here we longitudinally profile the early humoral immune response against SARS-CoV-2 in hospitalized coronavirus disease 2019 (COVID-19) patients and quantify levels of pre-existing immunity to OC43, HKU1 and 229E seasonal coronaviruses, and find a strong back-boosting effect to conserved but not variable regions of OC43 and HKU1 betacoronaviruses spike protein. However, such antibody memory boost to human coronaviruses negatively correlates with the induction of IgG and IgM against SARS-CoV-2 spike and nucleocapsid protein. Our findings thus provide evidence of immunological imprinting by previous seasonal coronavirus infections that can potentially modulate the antibody profile to SARS-CoV-2 infection.
The prolonged contagious period after viral infection in immunocompromised patients may affect how long precautions will be necessary to reduce further transmission. Replication-competent SARS-CoV-2 ...was detected for up to 61 days in patients who were immunocompromised by treatment for cancer.
Developing a researchable question is one of the challenging tasks a researcher encounters when initiating a project. Both, unanswered issues in current clinical practice or when experiences dictate ...alternative therapies may provoke an investigator to formulate a clinical research question. This article will assist researchers by providing step-by-step guidance on the formulation of a research question. This paper also describes PICO (population, intervention, control, and outcomes) criteria in framing a research question. Finally, we also assess the characteristics of a research question in the context of initiating a research project.
Due to differences in human and murine angiotensin converting enzyme 2 (ACE-2) receptor, initially available SARS-CoV-2 isolates could not infect mice. Here we show that serial passaging of ...USA-WA1/2020 strain in mouse lungs results in "mouse-adapted" SARS-CoV-2 (MA-SARS-CoV-2) with mutations in S, M, and N genes, and a twelve-nucleotide insertion in the S gene. MA-SARS-CoV-2 infection causes mild disease, with more pronounced morbidity depending on genetic background and in aged and obese mice. Two mutations in the S gene associated with mouse adaptation (N501Y, H655Y) are present in SARS-CoV-2 variants of concern (VoCs). N501Y in the receptor binding domain of viruses of the B.1.1.7, B.1.351, P.1 and B.1.1.529 lineages (Alpha, Beta, Gamma and Omicron variants) is associated with high transmissibility and allows VoCs to infect wild type mice. We further show that S protein mutations of MA-SARS-CoV-2 do not affect neutralization efficiency by human convalescent and post vaccination sera.
Hybrid immunity (vaccination + natural infection) to SARS-CoV-2 provides superior protection to re-infection. We performed immune profiling studies during breakthrough infections in mRNA-vaccinated ...hamsters to evaluate hybrid immunity induction. The mRNA vaccine, BNT162b2, was dosed to induce binding antibody titers against ancestral spike, but inefficient serum virus neutralization of ancestral SARS-CoV-2 or variants of concern (VoCs). Vaccination reduced morbidity and controlled lung virus titers for ancestral virus and Alpha but allowed breakthrough infections in Beta, Delta and Mu-challenged hamsters. Vaccination primed for T cell responses that were boosted by infection. Infection back-boosted neutralizing antibody responses against ancestral virus and VoCs. Hybrid immunity resulted in more cross-reactive sera, reflected by smaller antigenic cartography distances. Transcriptomics post-infection reflects both vaccination status and disease course and suggests a role for interstitial macrophages in vaccine-mediated protection. Therefore, protection by vaccination, even in the absence of high titers of neutralizing antibodies in the serum, correlates with recall of broadly reactive B- and T-cell responses.
Nuclear export of influenza A virus (IAV) mRNAs occurs through the nuclear pore complex (NPC). Using the Auxin-Induced Degron (AID) system to rapidly degrade proteins, we show that among the ...nucleoporins localized at the nucleoplasmic side of the NPC, TPR is the key nucleoporin required for nuclear export of influenza virus mRNAs. TPR recruits the TRanscription and EXport complex (TREX)-2 to the NPC for exporting a subset of cellular mRNAs. By degrading components of the TREX-2 complex (GANP, Germinal-center Associated Nuclear Protein; PCID2, PCI domain containing 2), we show that influenza mRNAs require the TREX-2 complex for nuclear export and replication. Furthermore, we found that cellular mRNAs whose export is dependent on GANP have a small number of exons, a high mean exon length, long 3' UTR, and low GC content. Some of these features are shared by influenza virus mRNAs. Additionally, we identified a 45 nucleotide RNA signal from influenza virus HA mRNA that is sufficient to mediate GANP-dependent mRNA export. Thus, we report a role for the TREX-2 complex in nuclear export of influenza mRNAs and identified RNA determinants associated with the TREX-2-dependent mRNA export.
Strongyloides hyperinfection syndrome is a rare manifestation caused by the Strongyloides stercoralis parasite and has mortality rates close to 90% if left untreated. Corticosteroids are commonly ...implicated as a trigger for hyperinfection syndrome in patients with Strongyloides autoinfection, and it has been suggested that even a single dose of corticosteroids can trigger hyperinfection syndrome. Here, we report a case of hyperinfection syndrome eight days after administering a single 8 mg dose of dexamethasone for fetal lung development before a late preterm, emergency cesarean section (C-section) delivery secondary to placental abruption.Prior to the C-section, the patient had been exhibiting signs of autoinfection syndrome, cough, and abdominal pain, for several months. Following corticosteroid administration, she had sequelae of Strongyloides hyperinfection syndrome, including gram-negative bacteremia, undulating fevers, protein wasting enteropathy, and hypersensitivity pneumonitis. Sputum cultures were positive for Strongyloides, and after treatment with ivermectin and albendazole, the patient fully recovered.Strongyloides hyperinfection syndrome is a documented consequence of short courses of corticosteroids. Still, this case is unique because the patient only received a single dose of corticosteroids before developing hyperinfection syndrome. Clinicians must recognize patients at risk for Strongyloides hyperinfection syndrome and understand the risks of administering corticosteroids to patients harboring the parasite.
•We present two cases of vaccine-induced disease in cancer patients.•History of recent vaccination can lead to expedited treatment.•It is unclear if treatment of infection reduces efficacy of the ...vaccine.
Vaccines containing live attenuated bacterial or viral organisms are currently being investigated as potential therapy for locally advanced or metastatic cancers. However, the use of such live organisms in an immunocompromised population, such as patients who recently or are currently receiving chemotherapy, raises the concern that these organisms can themselves disseminate and cause frank infection. We report a hereunto unreported phenomenon of anti-cancer vaccines (containing live attenuated organisms) leading to frank, disseminated infection. We submit that occurrence of this phenomenon must be watched for by all members of the interdisciplinary cancer treatment team.
New remains of
Propotamochoerus hysudricus
are described from localities of the Dhok Pathan and Nagri formations of the Middle Siwaliks of Pakistan.
Propotamochoerus hysudricus
is a moderate-sized ...extinct suid with comparatively larger cheek teeth, elongated first molar, and basal pillars. The
Propotamochoerus hysudricus
material described in this article is a good addition in the field of paleontology as these new remains comprise of the maxilla, mandibles, isolated incisors, and canine along with premolars and molars. The genus
Propotamochoerus
in the Siwaliks is represented only by a single species, i.e.,
Propotamochoerus hysudricus.
Its closest relative
Korynochoerus
is found in Eurasia. The age range of the species is from about 10 million to about 6 million years. The probable ancestor of
Propotamochoerus
is
Hyotherium
of Chinji times about 11 million years ago. The primitive genus
Propotamochoerus
was pretty near to the
Palaeochoerus
and was treated as a precursor of other suinae. Ancient Propotamochoeroid stock gave rise to three major groups, one leading to genera
Potamochoerus
and
Sus
, the other to the genera
Hippohyus
and
Sivahyus,
another leading to the genera
Microstonyx
,
Hippopotamodon
, and
Jhelumia.
The major difference between
Propotamochoerus hysudricus
and other species of the genus
Propotamochoerus
is mainly the dental morphology of premolars.
Influenza A viruses (IAVs) have a remarkable tropism in their ability to circulate in both mammalian and avian species. The IAV NS1 protein is a multifunctional virulence factor that inhibits the ...type I interferon host response through a myriad of mechanisms. How NS1 has evolved to enable this remarkable property across species and its specific impact in the overall replication, pathogenicity, and host preference remain unknown. Here we analyze the NS1 evolutionary landscape and host tropism using a barcoded library of recombinant IAVs. Results show a surprisingly great variety of NS1 phenotypes according to their ability to replicate in different hosts. The IAV NS1 genes appear to have taken diverse and random evolutionary pathways within their multiple phylogenetic lineages. In summary, the high evolutionary plasticity of this viral protein underscores the ability of IAVs to adapt to multiple hosts and aids in our understanding of its global prevalence.
Display omitted
•Influenza A NS1-mediated host tropism is versatile and constantly evolving•Phylogenetically related NS1 can display divergent phenotypic profiles•Avian-origin allele B NS1 efficiently replicates in a range of hosts•The library allows the study of NS1 fitness contribution within a viral population
Muñoz-Moreno et al. report that influenza A virus NS1 undergoes diverse and unpredictable evolutionary pathways based on its different phylogenetic lineages. A high-throughput approach using a barcoded library is used to test the interactions between NS1-recombinant viruses and to study their preference for specific or multiple hosts.
PDF
