Biology subjects
Publications and source records attributed to Mukesh, R..
We compared clinical disease, virus shedding and dissemination following genital MPXV clade Ia and Ib infections in Mastomys natalensis. MPXV clade Ib resulted in a milder clinical disease but a similar shedding profile to clade Ia. These findings indicate a prolonged pre-symptomatic or prodromal shedding period in clade Ib infections.
The transmission pattern of mpox has shifted from sporadic zoonotic outbreaks to sustained human-to-human spread. Epidemiological data indicate sexual contact as a crucial driver for efficient transmission and the associated devastating mpox outbreaks in recent years. However, our understanding of exact driving factors and transmission determinants is still limited. Here, we investigated MPXV clade Ia virus pathogenicity, shedding kinetics, and transmission potential in a prairie dog model (Cynomys ludovicianus). All tested mucosal inoculation routes (penile/preputial, vaginal, rectal, intranasal) resulted in a productive, systemic infection. Inoculation via urogenital routes generated the highest virus shedding and most severe clinical disease. A simulated sexual contact transmission resulted in 100% transmission efficiency with high virus shedding in sentinels on day 1, even before the onset of clinical signs. Our findings provide critical insights into mpox transmission, emphasizing the role of anogenital mucosal surfaces in facilitating rapid spread. These results advocate for a stronger focus on mucosal infection when evaluating countermeasures.
The ongoing outbreak of highly pathogenic avian influenza virus (HPAIV) subtype H5N1 in the U.S. poses a significant public health threat. To date, 70 human cases have been confirmed in the United States, including two severe cases and one fatality. While suitable animal models are crucial for predicting the potential pandemic risk of newly emerging pathogens in humans, studies investigating contemporary HPAIV H5N1 transmission dynamics remain limited. Here, we investigated the pathogenicity and transmission efficiency of three recent clade 2.3.4.4b H5N1 viruses isolated from a bovine, mountain lion, and a human case using Syrian hamsters. Intranasal inoculation with 104 TCID50 resulted in productive virus replication in the respiratory tract and shedding for all three isolates. Transmission studies showed limited efficiency via direct contact and airborne routes for all three isolates. Although overall transmission was inefficient, the human H5N1 isolate demonstrated relatively greater contact transmissibility than the bovine and mountain lion isolates. Taken together, our data demonstrate that the Syrian hamster model complements existing animal models for influenza A virus research and expands the resources available for investigating the pathogenicity, transmissibility, and efficacy of countermeasures against HPAIV H5N1. One sentence summaryHuman HPAIV H5N1 exhibits comparatively higher contact transmissibility than bovine and mountain lion isolates, despite limited overall transmission.
H5N1 influenza outbreaks in dairy cows necessitate studying potential transmission routes among livestock and to humans. We measured the stability of infectious H5N1 influenza virus in raw milk, wastewater, and on contaminated surfaces. We found relatively slow decay in milk, indicating that contaminated milk and fomites pose plausible transmission risks.
The emergence of the Omicron lineage represented a major genetic drift in SARS-CoV-2 evolution. This was associated with phenotypic changes including evasion of pre-existing immunity and decreased disease severity. Continuous evolution within the Omicron lineage raised concerns of potential increased transmissibility and/or disease severity. To address this, we evaluated the fitness and pathogenesis of contemporary Omicron variants XBB.1.5, XBB.1.16, EG.5.1, and JN.1 in the upper (URT) and lower respiratory tract (LRT). We compared in vivo infection in Syrian hamsters with infection in primary human nasal and lung epithelium cells and assessed differences in transmissibility, antigenicity, and innate immune activation. Omicron variants replicated efficiently in the URT but displayed limited pathology in the lungs compared to previous variants and failed to replicate in human lung organoids. JN.1 was attenuated in both URT and LRT compared to other Omicron variants and failed to transmit in the hamster model. Our data demonstrate that Omicron lineage evolution has favored increased fitness in the URT.