Skip to main content

Variable #DPP4 #expression in multiciliated cells of the #human #nasal #epithelium as a determinant for #MERS-CoV tropism

Image
By G.M.

Significance

Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic coronavirus that continues to cause periodic outbreaks in humans with a case-fatality rate of approximately 35%. MERS-CoV generally transmits poorly, but superspreading events are well documented. Efficient human-to-human transmission of respiratory viruses generally correlates with a tropism for the upper respiratory tract, but this tropism for MERS-CoV remains poorly understood. Characterizing the MERS-CoV tropism in the human upper respiratory tract is of critical importance to understand its epidemiology and pandemic potential of future MERS-CoV variants and other dipeptidyl peptidase 4 (DPP4)-utilizing coronaviruses present in animal reservoirs.


Abstract

Transmissibility of respiratory viruses is a complex viral trait that is intricately linked to tropism. Several highly transmissible viruses, including severe acute respiratory syndrome coronavirus 2 and Influenza viruses, specifically target multiciliated cells in the upper respiratory tract to facilitate efficient human-to-human transmission. In contrast, the zoonotic Middle East respiratory syndrome coronavirus (MERS-CoV) generally transmits poorly between humans, which is largely attributed to the absence of its receptor dipeptidyl peptidase 4 (DPP4) in the upper respiratory tract. At the same time, MERS-CoV epidemiology is characterized by occasional superspreading events, suggesting that some individuals can disseminate this virus effectively. Here, we utilized well-differentiated human pulmonary and nasal airway organoid-derived cultures to further delineate the respiratory tropism of MERS-CoV. We find that MERS-CoV replicated to high titers in both pulmonary and nasal airway cultures. Using single-cell messenger-RNA sequencing, immunofluorescence, and immunohistochemistry, we show that MERS-CoV preferentially targeted multiciliated cells, leading to loss of ciliary coverage. MERS-CoV cellular tropism was dependent on the differentiation of the organoid-derived cultures, and replication efficiency varied considerably between donors. Similarly, variable and focal expression of DPP4 was revealed in human nose tissues. This study indicates that the upper respiratory tract tropism of MERS-CoV may vary between individuals due to differences in DPP4 expression, providing an explanation for the unpredictable transmission pattern of MERS-CoV.

Source: Proceedings of the National Academy of Sciences of the United States of America, https://www.pnas.org/doi/10.1073/pnas.2410630122

____

Labels:

Comments

Post a Comment

Popular posts from this blog

#Neuroinvasive #Oropouche virus in a patient with #HIV from extra-Amazonian #Brazil

By G.M.
{Excerpt} A novel reassortant Oropouche virus (OROV) lineage (with medium [M], large [L], and small [S] RNA segments : M1L2S2) has driven Brazil's largest and most geographically widespread OROV epidemic , expanding beyond the endemic Amazon basin to establish local transmission across multiple Brazilian states and other previously unaffected Latin American countries . The rapid spread of this lineage underscores its evolutionary potential and reinforces its significance as a public health threat .1 Similar to chikungunya and Zika viruses, expanding arboviruses can exhibit unexpected clinical and epidemiological shifts , including vertical transmissions , neuroinvasive effects, and potentially fatal outcomes.2–4 Although OROV typically causes self-limited febrile illness, accumulating clinical and experimental evidence suggests neurotropic potential .5 This Correspondence describes the first confirmed case of neuroinvasive OROV infection caused by the emergent M1L2S2 lineage in ext...
Post a Comment
Read more »

No evidence of immune #exhaustion after repeated #SARS-CoV-2 #vaccination in vulnerable and healthy populations

By G.M.
Abstract Frequent SARS-CoV-2 vaccination in vulnerable populations has raised concerns that this may contribute to T cell exhaustion , which could negatively affect the quality of immune protection. Herein, we examined the impact of repeated SARS-CoV-2 vaccination on T cell phenotypic and functional exhaustion in frail older adults in long-term care (n = 23), individuals on immunosuppressive drugs (n = 10), and healthy adults (n = 43), in Canada . Spike-specific CD4+ and CD8+ T cell levels did not decline in any cohort following repeated SARS-CoV-2 vaccination, nor did the expression of exhaustion markers on spike-specific or total T cells increase. T cell production of multiple cytokines (i.e. polyfunctionality) in response to the spike protein of SARS-CoV-2 did not decline in any cohort following repeated vaccination. None of the cohorts displayed elevated levels of terminally differentiated T cells following multiple SARS-CoV-2 vaccinations. Thus, repeated SARS-CoV-2 vaccination was...
Post a Comment
Read more »

Chimeric #hemagglutinin and #M2 #mRNA #vaccine for broad #influenza subtype protection

By G.M.
Abstract Since multiple and unpredicted influenza viruses cause seasonal epidemics and even high-risk pandemics , developing a universal influenza vaccine is essential to provide broad protection against various influenza subtypes. Combined with the mRNA lipid nanoparticle-encapsulated (mRNA-LNP) vaccine platform and chimeric immunogen strategy , we developed a novel cocktail mRNA vaccine encoding chimeric HAs (cH5/1-BV, cH7/3) and intact M2 (termed Fluaxe), which confers broad protection against major circulating IAVs and IBVs , as well as highly pathogenic avian influenza . Two-dose intramuscular immunization of Fluaxe in mice elicited cross-reactive neutralizing antibodies , T cell responses, and long-lived immunity, resulting in robust protection against multiple lethal influenza virus infections and severe acute lung injuries . In particular, intramuscular administration stimulated systemic immunity together with a prominent lung tropism of memory cells . Moreover, Fluaxe immuniza...
Post a Comment
Read more »