Barcoded SARS-CoV-2 viruses define the impact of duration and route of exposure on the transmission bottleneck in a hamster model.

The transmission bottleneck, defined as the number of viruses shed from one host to infect another, is an important determinant of the rate of virus evolution and the level of immunity required to protect against virus transmission. Despite its importance, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission bottleneck remains poorly characterized. We adapted a SARS-CoV-2 reverse genetics system to generate a pool of >200 isogenic SARS-CoV-2 viruses harboring specific 6-nucleotide barcodes, infected donor hamsters with this pool, and exposed contact hamsters to paired infected donors, varying the duration and route of exposure.

Defining a highly conserved B cell epitope in the receptor binding motif of SARS-CoV-2 spike glycoprotein.

SARS-CoV-2 mRNA vaccines induce robust and persistent germinal centre (GC) B cell responses in humans. It remains unclear how the continuous evolution of the virus impacts the breadth of the induced GC B cell response. Using ultrasound-guided fine needle aspiration, we examined draining lymph nodes of nine healthy adults following bivalent booster immunization.

Immunogenicity and efficacy of XBB.1.5 rS vaccine against the EG.5.1 variant of SARS-CoV-2 in Syrian hamsters.

Unlabelled: The continued emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants necessitates updating coronavirus disease 2019 (COVID-19) vaccines to match circulating strains. The immunogenicity and efficacy of these vaccines must be tested in pre-clinical animal models. In Syrian hamsters, we measured the humoral and cellular immune response after immunization with the nanoparticle recombinant Spike (S) protein-based COVID-19 vaccine (Novavax, Inc.

Mucosal immunization with ChAd-SARS-CoV-2-S prevents sequential transmission of SARS-CoV-2 to unvaccinated hamsters.

COVID-19 vaccines have successfully reduced severe disease and death after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Nonetheless, COVID-19 vaccines are variably effective in preventing transmission and symptomatic SARS-CoV-2 infection. Here, we evaluated the impact of mucosal or intramuscular vaccine immunization on airborne infection and transmission of SARS-CoV-2 in Syrian hamsters.

Barcoded SARS-CoV-2 viruses define the impact of time and route of transmission on the transmission bottleneck in a Syrian hamster model.

The transmission bottleneck, defined as the number of viruses that transmit from one host to infect another, is an important determinant of the rate of virus evolution and the level of immunity required to protect against virus transmission. Despite its importance, SARS-CoV-2's transmission bottleneck remains poorly characterized, in part due to a lack of quantitative measurement tools. To address this, we adapted a SARS-CoV-2 reverse genetics system to generate a pool of >200 isogenic SARS-CoV-2 viruses harboring specific 6-nucleotide barcodes inserted in ORF10, a non-translated ORF.

Immunogenicity and efficacy of XBB.1.5 rS vaccine against EG.5.1 variant of SARS-CoV-2 in Syrian hamsters.

The continued emergence of SARS-CoV-2 variants necessitates updating COVID-19 vaccines to match circulating strains. The immunogenicity and efficacy of these vaccines must be tested in pre-clinical animal models. In Syrian hamsters, we measured the humoral and cellular immune response after immunization with the nanoparticle recombinant Spike (S) protein-based COVID-19 vaccine (Novavax, Inc.

Mucosal vaccine-induced cross-reactive CD8 T cells protect against SARS-CoV-2 XBB.1.5 respiratory tract infection.

A nasally delivered chimpanzee adenoviral-vectored severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine (ChAd-SARS-CoV-2-S) is currently used in India (iNCOVACC). Here, we update this vaccine by creating ChAd-SARS-CoV-2-BA.5-S, which encodes a prefusion-stabilized BA.

Characterization of the SARS-CoV-2 BA.5.5 and BQ.1.1 Omicron variants in mice and hamsters.

The continued evolution and emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have resulted in challenges to vaccine and antibody efficacy. The emergence of each new variant necessitates the need to re-evaluate and refine animal models used for countermeasure testing. Here, we tested a recently circulating SARS-CoV-2 Omicron lineage variant, BQ.

The Highly Conserved Stem-Loop II Motif Is Dispensable for SARS-CoV-2.

The stem-loop II motif (s2m) is an RNA structural element that is found in the 3' untranslated region (UTR) of many RNA viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Though the motif was discovered over 25 years ago, its functional significance is unknown. In order to understand the importance of s2m, we created viruses with deletions or mutations of the s2m by reverse genetics and also evaluated a clinical isolate harboring a unique s2m deletion.

A bivalent ChAd nasal vaccine protects against SARS-CoV-2 BQ.1.1 and XBB.1.5 infection and disease in mice and hamsters.

We previously described a nasally delivered monovalent adenoviral-vectored SARS-CoV-2 vaccine (ChAd-SARS-CoV-2-S, targeting Wuhan-1 spike [S]; iNCOVACC) that is currently used in India as a primary or booster immunization. Here, we updated the mucosal vaccine for Omicron variants by creating ChAd-SARS-CoV-2-BA.5-S, which encodes for a pre-fusion and surface-stabilized S protein of the BA.

Comprehensive genetic and phenotype analysis of 95 individuals with mosaic tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is a neurogenetic disorder due to loss-of-function TSC1 or TSC2 variants, characterized by tumors affecting multiple organs, including skin, brain, heart, lung, and kidney. Mosaicism for TSC1 or TSC2 variants occurs in 10%-15% of individuals diagnosed with TSC. Here, we report comprehensive characterization of TSC mosaicism by using massively parallel sequencing (MPS) of 330 TSC samples from a variety of tissues and fluids from a cohort of 95 individuals with mosaic TSC.

The highly conserved stem-loop II motif is dispensable for SARS-CoV-2.

Unlabelled: The stem-loop II motif (s2m) is a RNA structural element that is found in the 3' untranslated region (UTR) of many RNA viruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Though the motif was discovered over twenty-five years ago, its functional significance is unknown. In order to understand the importance of s2m, we created viruses with deletions or mutations of the s2m by reverse genetics and also evaluated a clinical isolate harboring a unique s2m deletion.

Diagnosis of Mosaic Tuberous Sclerosis Complex Using Next-Generation Sequencing of Subtle or Unusual Cutaneous Findings.

Skin findings can be critical to determining whether a patient with lymphangioleiomyomatosis (LAM), a progressive pulmonary disease that predominantly affects adult women, has sporadic LAM or LAM in association with tuberous sclerosis complex (TSC). Three individuals with LAM underwent evaluation for TSC-associated mucocutaneous and internal findings. We used our previously published algorithm to confirm the clinical suspicion for mosaicism and guide the selection of tissue specimens and genetic workup.

mRNA Vaccine Mitigates SARS-CoV-2 Infections and COVID-19.

The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified in December of 2019 and is responsible for millions of infections and deaths across the globe. Vaccination against SARS-CoV-2 has proven effective to contain the spread of the virus and reduce disease. The production and distribution of these vaccines occurred at a remarkable pace, largely through the employment of the novel mRNA platform.

Is the Glycoprotein Responsible for the Differences in Dispersal Rates between Lettuce Necrotic Yellows Virus Subgroups?

is a type of species in the genus and appears to be endemic to Australia and Aotearoa New Zealand (NZ). The population of lettuce necrotic yellows virus (LNYV) is made up of two subgroups, SI and SII. Previous studies demonstrated that SII appears to be outcompeting SI and suggested that SII may have greater vector transmission efficiency and/or higher replication rate in its host plant or insect vector.

mRNA-1273 and Ad26.COV2.S vaccines protect against the B.1.621 variant of SARS-CoV-2.

Background: Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019, viral variants with greater transmissibility or immune-evasion properties have arisen, which could jeopardize recently deployed vaccine- and antibody-based countermeasures.

Methods: Here, we evaluated in mice and hamsters the efficacy of a pre-clinical version of the Moderna mRNA vaccine (mRNA-1273) and the Johnson & Johnson recombinant adenoviral-vectored vaccine (Ad26.COV2.

The highly conserved stem-loop II motif is important for the lifecycle of astroviruses but dispensable for SARS-CoV-2.

The stem-loop II motif (s2m) is an RNA element present in viruses from divergent viral families, including astroviruses and coronaviruses, but its functional significance is unknown. We created deletions or substitutions of the s2m in astrovirus VA1 (VA1), classic human astrovirus 1 (HAstV1) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For VA1, recombinant virus could not be rescued upon partial deletion of the s2m or substitutions of G-C base pairs.

Ultrasensitive profiling of UV-induced mutations identifies thousands of subclinical facial tumors in tuberous sclerosis complex.

BackgroundTuberous sclerosis complex (TSC) is a neurogenetic syndrome due to loss-of-function mutations in TSC2 or TSC1, characterized by tumors at multiple body sites, including facial angiofibroma (FAF). Here, an ultrasensitive assessment of the extent and range of UV-induced mutations in TSC facial skin was performed.MethodsA multiplex high-sensitivity PCR assay (MHPA) was developed, enabling mutation detection at extremely low (<0.