Journal of Medical Virology最新文献

The evolution of SARS-CoV-2, which limits public control and treatment, seems to have occurred through multiple mechanisms, including recombination of cocirculating strains in hosts. However, insufficient experimental data have been obtained after coinfection. Therefore, we investigated the emergence of variants after coinfection with parental SARS-CoV-2 and the SARS-CoV-2 Delta. We found that fewer (approximately 50%) mutations accumulated in Calu-3 cells than in other cells after serial passaging. Previously, we established a long-term replication mouse model by infecting Calu-3 cell-derived xenograft tumors with SARS-CoV-2. Here, we utilized our model to investigate the outcome after coinfection. More diverse viral mutations, along with multiple high-frequency simultaneous mutations, were discovered in the tumors than during cell passaging. Viral isolates from the tumors showed no cytopathic effects and formed much smaller plaques. Phylogenetic analysis suggested that the genetic makeup of the variants remained largely the same as that of parental SARS-CoV-2 rather than the SARS-CoV-2 Delta. Viral challenge revealed that the isolates were less lethal than the parental SARS-CoV-2 and SARS-CoV-2 Delta strains. These findings suggest that parental SARS-CoV-2 predominates over the SARS-CoV-2 Delta when coinfected, but the SARS-CoV-2 Delta contributes to the evolution of parental SARS-CoV-2 variants toward better host adaptation without recombination.

HPV viral E6 and E7 onco-proteins play a well-known role in carcinogenesis. Host genomic alterations also play a key role in the development of HPV-related oropharyngeal cancer and have been under-recognized. We describe a case series of 6 metastatic/locoregionally recurrent HPVOPSCC patients with FGFR alterations. HPVOPSCC presents with distinct pattern of spread both temporally and sites of recurrence compared to  non-HPV-related oropharyngeal cancer. Identification and reporting of genomic alterations in HPV are crucial to the understanding of disease biology and could aid in development of novel therapeutics for these patients. In addition, use of circulating tumor DNA may lead to early detection and supplement imaging in the follow up of these patients. Loco-regional treatments may also play a key role in the management of metastatic HPV OPSCC depending on the pattern of presentation. Our case series highlights all these novelties that could lead to better treatment outcomes.

Elucidating the detailed features of emerging SARS-CoV-2 strains both in vitro and in vivo is indispensable for the development of effective vaccines or drugs against viral infection. We thoroughly characterized the virological and pathogenic features of eight different pandemic SARS-CoV-2 strains, from the WT strain to current circulating sublineage EG.5.1, both in vitro and in vivo. Besides detailed virological features observed in Vero E6 cells, the Omicron variants, from BA.1 to EG.5.1, exhibited enhanced infectious effects to upper respiratory tract in K18 human angiotensin-converting enzyme (ACE2) (K18 hACE2) transgenic mice. Both XBB.1.9.1 and EG.5.1 presented stronger tropism to brain, which could be the main reason for the increased lethal effects on mice. In addition, the pathogenesis comparisons among all these viruses in C57BL/6JGpt mice indicated that Omicron variant BA.1 and two new sublineages XBB.1.9.1 and EG.5.1 possessed dual tropisms to both human and mice, which were further confirmed by subsequent bioinformatic analyses and actual affinity comparison between viral RBDs and mouse or human receptor ACE2. Furthermore, the immunocompromised BKS-db mice were found to be more susceptible to Omicron strains compared to C57BL/6JGpt mice, which revealed that viral infectivity was determined by both its affinity to the host receptor and host immunocompetence. Thus, this study not only contributes to a systematic understanding of the pathogenic features of SARS-CoV-2 in mice, but also provides new insights to combat potential future surges of new SARS-CoV-2 variants.

Hepatitis B virus reactivation (HBVr) can be a serious clinical complication that has not been fully characterized in terms of the drugs associated with this adverse effect. Leveraging the expansive data available in the FDA Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report (JADER) databases, we conducted a retrospective analysis to identify drugs significantly linked to HBVr using three disproportionality analyses. Our study identified 44 drugs associated with HBVr, of which 35 did not have warnings in their product labels. The majority of these drugs were antineoplastic and immunomodulating agents, with a tendency for early occurrence of HBVr, particularly among antineoplastic agents and systemic corticosteroids. Additionally, entecavir, tenofovir disoproxil and tenofovir alafenamide demonstrated better safety profiles in preventing HBVr. These findings enhance our understanding of the demographic characteristics of patients at risk for HBVr, the drugs that pose a high risk for HBVr, the timing of such events, and the appropriate preventive medications. This knowledge contributes to the development of better prevention and treatment strategies, ultimately optimizing patient outcomes.

Stimulator of interferon genes (STING) is an endoplasmic reticulum (ER) protein that plays a crucial role in cytosolic DNA-mediated innate immunity. Both STING agonists and antagonists have demonstrated their ability to enhance mouse survival against coronavirus, however, the physiological role of endogenous STING in coronavirus infection remains unclear. Our research unveils that STING inhibits coronavirus replication by impeding the formation of the ER-derived double-membrane vesicles (DMVs), the organelles in which coronavirus replicates. We found that STING was still capable of inhibiting coronavirus OC43 infection in cells, regardless of the knockout of cGAS or MAVS, or blocking type I interferon receptor. Moreover, STING disrupted the interaction between two crucial proteins, NSP4 and NSP6, involved in DMV formation, leading to the disruption of DMV formation. Taken together, our study sheds light on a novel antiviral role of STING in coronavirus infection, elucidating how it disrupts the formation of viral replication organelles, thereby impeding the replication process.

The 2022–2024 outbreak of MPOX is an important worldwide public health issue that has triggered significant concerns in the scientific community. MPOX is caused by monkeypox virus (MPXV) belonging to the Poxviridae family. The study of MPXV presents a multifaceted challenge due to the diverse viral formThis study was supported by ISIDORe consortium and Agencia Estatal de Investigación.s produced by this pathogen. Notably the intracellular mature viruses (MVs) primarily contribute to localized lesions and host-to-host transmission, while the extracellular enveloped viruses (EVs) are associated with systemic infection. Clinically, MPOX manifests as a vesiculopustular rash that initially emerges on the face and trunk, subsequently spreading throughout the body, with heightened severity observed in immunocompromised individuals. Results obtained in this manuscript indicate that the 2022 outbreak MPXV has a significantly slower viral cycle compared with previous Clade II strains, with WRAIR 7-61 being more intermediate and USA 2003 producing highest viral titers. Additionally, proteomic and phospho-proteomic analysis displays differences in protein expression between these three strains. These findings highlight key differences between the current Lineage B.1 MPXV and previous strains. Further studies will be undertaken to demonstrate if these differences are important for the apparent increased human-to-human transmission mechanisms observed in the Clade IIb MPXV outbreak.