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1.
Nat Microbiol ; 9(5): 1231-1243, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38649413

RESUMEN

The 2022 mpox virus (MPXV) outbreak was sustained by human-to-human transmission; however, it is currently unclear which factors lead to sustained transmission of MPXV. Here we present Mastomys natalensis as a model for MPXV transmission after intraperitoneal, rectal, vaginal, aerosol and transdermal inoculation with an early 2022 human outbreak isolate (Clade IIb). Virus shedding and tissue replication were route dependent and occurred in the presence of self-resolving localized skin, lung, reproductive tract or rectal lesions. Mucosal inoculation via the rectal, vaginal and aerosol routes led to increased shedding, replication and a pro-inflammatory T cell profile compared with skin inoculation. Contact transmission was higher from rectally inoculated animals. This suggests that transmission might be sustained by increased susceptibility of the anal and genital mucosae for infection and subsequent virus release.


Asunto(s)
Membrana Mucosa , Infecciones por Poxviridae , Esparcimiento de Virus , Animales , Femenino , Membrana Mucosa/virología , Infecciones por Poxviridae/transmisión , Infecciones por Poxviridae/virología , Infecciones por Poxviridae/veterinaria , Humanos , Replicación Viral , Modelos Animales de Enfermedad , Roedores/virología , Masculino , Ratas , Vagina/virología , Brotes de Enfermedades
2.
Elife ; 122024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38416804

RESUMEN

It remains poorly understood how SARS-CoV-2 infection influences the physiological host factors important for aerosol transmission. We assessed breathing pattern, exhaled droplets, and infectious virus after infection with Alpha and Delta variants of concern (VOC) in the Syrian hamster. Both VOCs displayed a confined window of detectable airborne virus (24-48 hr), shorter than compared to oropharyngeal swabs. The loss of airborne shedding was linked to airway constriction resulting in a decrease of fine aerosols (1-10 µm) produced, which are suspected to be the major driver of airborne transmission. Male sex was associated with increased viral replication and virus shedding in the air. Next, we compared the transmission efficiency of both variants and found no significant differences. Transmission efficiency varied mostly among donors, 0-100% (including a superspreading event), and aerosol transmission over multiple chain links was representative of natural heterogeneity of exposure dose and downstream viral kinetics. Co-infection with VOCs only occurred when both viruses were shed by the same donor during an increased exposure timeframe (24-48 hr). This highlights that assessment of host and virus factors resulting in a differential exhaled particle profile is critical for understanding airborne transmission.


Asunto(s)
COVID-19 , SARS-CoV-2 , Cricetinae , Animales , Masculino , Mesocricetus , Aerosoles y Gotitas Respiratorias
3.
Sci Rep ; 14(1): 3381, 2024 02 09.
Artículo en Inglés | MEDLINE | ID: mdl-38336916

RESUMEN

The intestinal microbiome plays an important role in mammalian health, disease, and immune function. In light of this function, recent studies have aimed to characterize the microbiomes of various bat species, which are noteworthy for their roles as reservoir hosts for several viruses known to be highly pathogenic in other mammals. Despite ongoing bat microbiome research, its role in immune function and disease, especially the effects of changes in the microbiome on host health, remains nebulous. Here, we describe a novel methodology to investigate the intestinal microbiome of captive Jamaican fruit bats (Artibeus jamaicensis). We observed a high degree of individual variation in addition to sex- and cohort-linked differences. The intestinal microbiome was correlated with intestinal metabolite composition, possibly contributing to differences in immune status. This work provides a basis for future infection and field studies to examine in detail the role of the intestinal microbiome in antiviral immunity.


Asunto(s)
Quirópteros , Microbioma Gastrointestinal , Humanos , Animales , Femenino , Masculino , Jamaica , Caracteres Sexuales , Mamíferos , Metaboloma
4.
Nat Commun ; 14(1): 6592, 2023 10 18.
Artículo en Inglés | MEDLINE | ID: mdl-37852960

RESUMEN

Limited data is available on the effect of vaccination and previous virus exposure on the nature of SARS-CoV-2 transmission and immune-pressure on variants. To understand the impact of pre-existing immunity on SARS-CoV-2 airborne transmission efficiency, we perform a transmission chain experiment using naïve, intranasally or intramuscularly AZD1222 vaccinated, and previously infected hamsters. A clear gradient in transmission efficacy is observed: Transmission in hamsters vaccinated via the intramuscular route was reduced over three airborne chains (approx. 60%) compared to naïve animals, whereas transmission in previously infected hamsters and those vaccinated via the intranasal route was reduced by 80%. We also find that the Delta B.1.617.2 variant outcompeted Omicron B.1.1.529 after dual infection within and between hosts in naïve, vaccinated, and previously infected transmission chains, yet an increase in Omicron B.1.1.529 competitiveness is observed in groups with pre-existing immunity against Delta B.1.617.2. This correlates with an increase in the strength of the humoral response against Delta B.1.617.2, with the strongest response seen in previously infected animals. These data highlight the continuous need to improve vaccination strategies and address the additional evolutionary pressure pre-existing immunity may exert on SARS-CoV-2.


Asunto(s)
COVID-19 , Vacunas , Animales , Cricetinae , Humanos , COVID-19/prevención & control , ChAdOx1 nCoV-19 , SARS-CoV-2
5.
bioRxiv ; 2023 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-36032963

RESUMEN

It remains poorly understood how SARS-CoV-2 infection influences the physiological host factors important for aerosol transmission. We assessed breathing pattern, exhaled droplets, and infectious virus after infection with Alpha and Delta variants of concern (VOC) in the Syrian hamster. Both VOCs displayed a confined window of detectable airborne virus (24-48 h), shorter than compared to oropharyngeal swabs. The loss of airborne shedding was linked to airway constriction resulting in a decrease of fine aerosols (1-10µm) produced, which are suspected to be the major driver of airborne transmission. Male sex was associated with increased viral replication and virus shedding in the air. Next, we compared the transmission efficiency of both variants and found no significant differences. Transmission efficiency varied mostly among donors, 0-100% (including a superspreading event), and aerosol transmission over multiple chain links was representative of natural heterogeneity of exposure dose and downstream viral kinetics. Co-infection with VOCs only occurred when both viruses were shed by the same donor during an increased exposure timeframe (24-48 h). This highlights that assessment of host and virus factors resulting in a differential exhaled particle profile is critical for understanding airborne transmission.

6.
Viruses ; 14(9)2022 09 11.
Artículo en Inglés | MEDLINE | ID: mdl-36146818

RESUMEN

An ongoing monkeypox outbreak in non-endemic countries has resulted in the declaration of a public health emergency of international concern by the World Health Organization (WHO). Though monkeypox has long been endemic in regions of sub-Saharan Africa, relatively little is known about its ecology, epidemiology, and transmission. Here, we consider the relevant research on both monkeypox and smallpox, a close relative, to make inferences about the current outbreak. Undetected circulation combined with atypical transmission and case presentation, including mild and asymptomatic disease, have facilitated the spread of monkeypox in non-endemic regions. A broader availability of diagnostics, enhanced surveillance, and targeted education, combined with a better understanding of the routes of transmission, are critical to identify at-risk populations and design science-based countermeasures to control the current outbreak.


Asunto(s)
Mpox , Viruela , Virus de la Viruela , Brotes de Enfermedades , Humanos , Monkeypox virus/genética , Viruela/prevención & control
7.
bioRxiv ; 2022 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-35982658

RESUMEN

Omicron has demonstrated a competitive advantage over Delta in vaccinated people. To understand this, we designed a transmission chain experiment using naïve, intranasally (IN) or intramuscularly (IM) vaccinated, and previously infected (PI) hamsters. Vaccination and previous infection protected animals from disease and virus replication after Delta and Omicron dual challenge. A gradient in transmission blockage was observed: IM vaccination displayed moderate transmission blockage potential over three airborne chains (approx. 70%), whereas, IN vaccination and PI blocked airborne transmission in >90%. In naïve hamsters, Delta completely outcompeted Omicron within and between hosts after dual infection in onward transmission. Although Delta also outcompeted Omicron in the vaccinated and PI transmission chains, an increase in Omicron competitiveness was observed in these groups. This correlated with the increase in the strength of the humoral response against Delta, with the strongest response seen in PI animals. These data highlight the continuous need to assess the emergence and spread of novel variants in populations with pre-existing immunity and address the additional evolutionary pressure this may exert on the virus.

8.
Viruses ; 14(3)2022 03 06.
Artículo en Inglés | MEDLINE | ID: mdl-35336950

RESUMEN

The emergence of SARS-CoV-2 in the human population and the resulting COVID-19 pandemic have led to the development of various diagnostic tests. The OraSure InteliSwab™ COVID-19 Rapid Test is a recently developed and FDA emergency use-authorized rapid antigen-detecting test that functions as a lateral flow device targeting the nucleocapsid protein. Due to SARS-CoV-2 evolution, there is a need to evaluate the sensitivity of rapid antigen-detecting tests for new variants, especially variants of concern such as Omicron. In this study, the sensitivity of the OraSure InteliSwab™ Test was investigated using cultured strains of the known variants of concern (VOCs, Alpha, Beta, Gamma, Delta, and Omicron) and the ancestral lineage (lineage A). Based on dilution series in cell culture medium, an approximate limit of detection for each variant was determined. The OraSure InteliSwab™ Test showed an overall comparable performance using recombinant nucleocapsid protein and different cultured variants, with recorded limits of detection ranging between 3.77 × 105 and 9.13 × 105 RNA copies/mL. Finally, the sensitivity was evaluated using oropharyngeal swabs from Syrian golden hamsters inoculated with the six VOCs. Ultimately, the OraSure InteliSwab™ COVID-19 Rapid Test showed no decrease in sensitivity between the ancestral SARS-CoV-2 strain and any VOCs including Omicron.


Asunto(s)
COVID-19 , SARS-CoV-2 , COVID-19/diagnóstico , Humanos , Proteínas de la Nucleocápside/genética , Pandemias , SARS-CoV-2/genética
9.
medRxiv ; 2022 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-35169818

RESUMEN

The emergence of SARS-CoV-2 in the human population and the resulting COVID-19 pandemic has led to the development of various diagnostic tests. The OraSure InteliSwab ® COVID-19 Rapid Test is a recently developed and FDA emergency use authorized rapid antigen-detecting test that functions as a lateral flow device targeting the nucleocapsid protein. Due to SARS-CoV-2 evolution, there is a need to evaluate the sensitivity of rapid antigen-detecting tests for new variants, especially variants of concern like Omicron. In this study, the sensitivity of the OraSure InteliSwab ® Test was investigated using cultured strains of the known variants of concern (VOCs, Alpha, Beta, Gamma, Delta, and Omicron) and the ancestral lineage (lineage A). Based on dilution series in cell culture medium, an approximate limit of detection for each variant was determined. The OraSure InteliSwab ® Test showed an overall comparable performance using recombinant nucleocapsid protein and different cultured variants with recorded limits of detection ranging between 3.77 × 10 5 and 9.13 × 10 5 RNA copies/mL. Finally, the sensitivity was evaluated using oropharyngeal swabs from Syrian golden hamsters inoculated with the 6 VOCs. Ultimately, the OraSure InteliSwab ® COVID-19 Rapid Test showed no decrease in sensitivity between the ancestral SARS-CoV-2 strain and any VOCs including Omicron.

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