Aug 2026· Virology· Vol 624, pp.
111036
· 0 citations· 41 references
Medicine
TL;DR
The findings demonstrate that the pathogenicity of the Omicron subvariants has not been fully attenuated in the absence of pre-existing immunity, since they caused severe lung disease in immunologically naïve macaques and their enhanced propagation in the upper airway likely facilitates efficient transmission among humans.
Abstract
Since the emergence of the SARS-CoV-2 Omicron variant, decreased morbidity and mortality relative to early strains have been widely reported. However, the virological characteristics of recent subvariants dominating the post-pandemic era remain to be fully elucidated. In the present study, the intrinsic pathogenicities of the Omicron subvariants JN.1, EG.5.1, and BA.2.86.1 were investigated using an immunologically naïve cynomolgus macaque model. All three variants exhibited robust replication in the upper respiratory tract, surpassing the viral titers observed with the early Wuhan strain. Omicron subvariant infection caused prolonged fever and sustained viral shedding in the nasal mucosa for at least seven days, indicating enhanced adaptation to upper airway tissues. Despite this shift in viral replication tropism, histological analysis showed that these variants retained the characteristics to induce lower respiratory tract disease. All infected macaques developed bronchopneumonia characterized by cellular exudates in the alveolar spaces. The histological scores were comparable to those observed with the early strain. These findings demonstrate that the pathogenicity of the Omicron subvariants has not been fully attenuated in the absence of pre-existing immunity, since they caused severe lung disease in immunologically naïve macaques. Furthermore, their enhanced propagation in the upper airway likely facilitates efficient transmission among humans. The continuous circulation of SARS-CoV-2 variants underscores the necessity of ongoing surveillance of viral gene variations and the maintenance of protective immunity in vulnerable populations.
This study provides direct experimental evidence for a pronounced attenuation in pathogenicity along the evolutionary trajectory from Wild-type through Delta to Omicron EG.5.5, and offers crucial insights for risk assessment of emerging variants.
Xiaofang Peng, Qi Zhang, Pingping Zhou et al.· Frontiers in Immunology· 0 citations
It is shown that a Wuhan-lineage-based multi-antigen VLP vaccine can provide cross-protection against an antigenically divergent SARS-CoV-2 variant that is not fully explained by detectable serum neutralizing activity alone, suggesting the importance of integrated immune responses involving humoral, cellular, and local immune mechanisms.
Seung-Ji Kim, Howon Kim, Seung-Eun Son et al.· Vaccine· 0 citations
Tracking SARS-CoV-2 variants revealed the predominance of the JN.1 sublineage of Omicron with generally mild symptoms, highlighting the need for robust, ongoing genomic surveillance integrated with epidemiological data to enable early detection of emerging variants and strengthen control strategies.
P. Rao, S. Ganju, Lata R. Chandel· Journal of Clinical and Diag...· 0 citations
Highly pathogenic avian influenza H5NX clade 2.3.4.4b viruses continue to circulate globally. Reintroduction of Eurasian lineage viruses into North America and reassortment with endemic low pathogenicity strains have resulted in new genotypes, including D1.2. To assess pathogenicity and cellular tropism, we intranasally inoculated genotype D1.2 virus into pigs. We isolated virus from nasal secretions from most inoculated animals for multiple days. At 5 days postinoculation, PCR and immunohistochemistry detected virus in musculoskeletal, respiratory, digestive, lymphatic, and nervous systems, and virus was isolated from meat juice. At 35 days postinoculation, we detected viral antigen and low levels of RNA in the brain of an animal with lesions consistent with a viral etiology and found viral antigen in the ethmoid of 2 animals. Consistent detection in nasal swab specimens, combined with subclinical respiratory infection, suggest that identifying infection in commercial swine without overt respiratory signs could be difficult.
Hannah Seger, Amy L. Baker, Alexandra C. Buckley et al.· Emerging Infectious Diseases· 0 citations
Higher order protein structural predictions suggested that the putative epistatic interactions among E180V, G184V, and G252V, D253G may be associated with S protein folding and structural stability.
M. Jogi, Sristy Shikha, Pushpendra Singh et al.· Frontiers in Immunology· 0 citations
The ability of respiratory viruses to exploit host immune responses to promote transmission is a defining feature of pandemics. SARS-CoV-2 remains a major global public health threat because of its persistent evolution and capacity to counteract evolving immune defenses. Although the immune evasion properties of the SARS-CoV-2 Spike protein are well characterized, the contributions of other viral proteins to transmission remain poorly understood. Here, we used the infant mouse model to define the role of the accessory protein ORF8 in SARS-CoV-2 spread. We demonstrate that ORF8 supports efficient upper respiratory tract (URT) infection, infectious virus shedding, and host-to-host transmission. Mice infected with a recombinant SARS-CoV-2 strain lacking ORF8 (rΔORF8) had less infectious virus recovered from URT tissues and nasal secretions and transmitted less efficiently than mice infected with the isogenic ancestral strain rWA-1, which contains an intact ORF8. Recombinant viruses encoding naturally occurring ORF8 mutations exhibited distinct transmission phenotypes, with ORF8-deficient viruses resembling rΔORF8. Infection with ORF8-sufficient viruses induced greater macrophage recruitment, inflammatory cytokine production, and type-I interferon (IFN-I) signaling programs than ORF8-deficient viruses. Intranasal IFNβ supplementation partially restored URT shedding by rΔORF8-infected mice and rescued transmission to contacts, whereas blockade of the type I interferon receptor (IFNAR) in rWA-1-infected index mice reduced contact infection and transmission. Together, these findings demonstrate that ORF8 promotes SARS-CoV-2 transmission by engaging an IFN-I-associated inflammatory and secretory program in the URT that supports virus shedding from the infected host. These data identify ORF8 as a viral determinant of host mucosal responses that promote contagiousness. Importance Efficient host-to-host transmission underlies the success of respiratory viruses. Although SARS-CoV-2 research has largely focused on the Spike protein, accessory proteins can also shape viral fitness and spread. We previously identified ORF8 as a determinant of SARS-CoV-2 transmission. Here we show that ORF8 promotes SARS-CoV-2 infectious viral shedding and transmission by engaging IFN-I-associated inflammatory and secretory responses in the URT. These findings reveal how a SARS-CoV-2 accessory protein can exploit mucosal antiviral responses to increase host contagiousness.
G. Ciabattoni, Stacey Bartlett, M. McGrath et al.· bioRxiv· 0 citations