Everolimus reduces BK polyomavirus infection by suppressing its replication and spread of infection

Studies analyzing the relationship between BK polyomavirus (BKV) or JC polyomavirus (JCV) infection and kidney transplant (KT) long term clinical outcomes are scarce. Therefore, we evaluated this relationship in a single-center retrospective cohort of 288 KT patients followed for 45.4(27.5; 62.5) months.Detection of BKV viremia in two consecutive analyses led to discontinuation of antimetabolite and initiation of mammalian target of rapamycin inhibitor.Outcome data included de novo BKV and/or JCV viremia and/or viruria after KT, death-censored graft survival and patient survival. BKV viruria and viremia were detected in 42.4% and 22.2% of KT recipients, respectively. BKV viremic patients had higher urinary BKV viral loads at the onset of viruria, when compared to nonviremic patients (7 log 10 vs. 4.9 log 10 cp/mL, p < 0.001). JCV viruria was identified in 38.5% of KT patients; the 5.9% of KT recipients who developed JCV viremia had higher JCV urinary viral loads at the onset of viruria, when compared to non-viremic patients (5.3 vs. 3.7 log 10 cp/mL, p = 0.034). No differences were found in estimated glomerular filtration rate at the end of follow up, when comparing BKV or JCV viruric or viremic patients with nonviremic patients. No association was found between JCV or BKV viruria or viremia and death/graft failure. Therefore, higher BKV urinary viral loads at the onset could serve as an early maker of over immunosuppression. JCV and BKV replication was not associated with inferior clinical outcomes in KT patients with the abovementioned immunosuppression strategy.

Section: Discussioncontrasting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Detection of JCV or BKV viruria and viremia after kidney transplantation is not associated with unfavorable outcomes

Querido

Weigert

Pinto

et al. 2023

“…38 In addition, several studies have found that Z08 can control the replication of polyomavirus and cytomegalovirus. 39,40 However, the correlation between Z25 and Z08 and CMPK2 has not been reported.…”

Section: Discussionmentioning

confidence: 99%

Drugs targeting CMPK2 inhibit pyroptosis to alleviate severe pneumonia caused by multiple respiratory viruses

Tang,

Mao,

Ruan

et al. 2024

Severe pneumonia caused by respiratory viruses has become a major threat to humans, especially with the SARS‐CoV‐2 outbreak and epidemic. The aim of this study was to investigate the universal molecular mechanism of severe pneumonia induced by multiple respiratory viruses and to search for therapeutic strategies targeting this universal molecular mechanism. The common differential genes of four respiratory viruses, including respiratory syncytial virus (RSV), rhinovirus, influenza, and SARS‐CoV‐2, were screened by GEO database, and the hub gene was obtained by Sytohubba in Cytoscape. Then, the effect of hub genes on inflammasome and pyrodeath was investigated in the model of RSV infection in vitro and in vivo. Finally, through virtual screening, drugs targeting the hub gene were obtained, which could alleviate severe viral pneumonia in vitro and in vivo. The results showed that CMPK2 is one of the hub genes after infection by four respiratory viruses. CMPK2 activates the inflammasome by activating NLRP3, and promotes the releases of inflammatory factors interleukin (IL)‐1β and IL‐18 to induce severe viral pneumonia. Z25 and Z08 can reduce the expression level of CMPK2 mRNA and protein, thereby inhibiting NLRP3 and alleviating the development of severe viral pneumonia. In conclusion, the inflammatory response mediated by CMPK2 is the common molecular mechanism of severe pneumonia induced by viral infection, and Z25 and Z08 can effectively alleviate viral infection and severe pneumonia through this mechanism.

“…Vero cells were used to isolate and propagate HSV. 11 HepG2 hepatoblastoma cells, A549 lung cancer cells, and human embryo lung (HEL) cells were used for the cell tropism assay, [12][13][14] and the isolates were typed using a microtrack assay and DNA restriction endonuclease analysis. 15 One infant (case 1) was born to a mother with no evidence of genital herpes or genital lesions at delivery.…”

Section: Methodsmentioning

confidence: 99%

“…The clinical information obtained at UAB for 13 cases with no UL13 mutation (Isolate Nos. 1,2,9,12,13,16,18,19,22,24,28,29,31) and those of three cases with UL13 mutation (Cases No. 3,4,5) are presented below.…”

Section: (B) (A) (C) (D)mentioning

confidence: 99%

Vertical mother‐to‐infant transmission of herpes simplex virus 2 is correlated with tropism due to mutations in viral UL13

Shiraki,

Daikoku,

Prichard

et al. 2024

Self Cite

Although neonates are commonly exposed to vaginal herpes simplex virus (HSV)‐2, neonatal herpes is rare. Therefore, we analyzed paired infant and maternal HSV‐2 isolates from two cases of mother‐to‐infant transmission to identify viral factors contributing to vertical transmission. Sixteen infant isolates with neonatal herpes and 27 genital isolates in their third trimester were included. The infant isolates were significantly more temperature‐independent than the maternal isolates. Sequence comparison revealed viral UL13 protein kinase (UL13‐PK) mutation in the infant isolates in both cases. In the expanded cohort, infant isolates (5/18) had significantly more UL13‐PK mutations than genital isolates (1/29). Isolates within 8 days post‐birth (3/4) had a significantly higher frequency of UL13‐PK mutation than those after 9 days (2/14), suggesting a close association between UL13‐PK mutations and vertical transmission. Elongation factor 1‐delta was identified as a target of UL13‐PK by proteomic analysis of UL13‐PK‐positive and ‐negative HepG2 cells. The mixed infant isolates with the intact and mutated UL13‐PK conferred altered cell tropism, temperature independence adapting to fetal temperature, and better growth properties in Vero and hepatoblastoma HepG2 cells than in HSV‐2 with intact and mutated UL13‐PK alone, indicating that viral UL13‐PK mutation is essential for vertical HSV‐2 transmission.