Platelets are considered as significant players in innate and adaptive immune responses. The adhesion molecules they express, including P-selectin, CD40L, and CD42b, facilitate interactions with many cellular effectors. Upon interacting with a pathogen, platelets rapidly express and enhance their adhesion molecules, and secrete cytokines and chemokines. A similar phenomenon occurs after exposure of platelets to thrombin, an agonist extensively used for in vitro activation of these cells. It was recently reported that the dengue virus not only interacts with platelets but possibly infects them, which triggers an increased expression of adhesion molecule P-selectin as well as secretion of IL-1β. In the present study, surface molecules of platelets like CD40L, CD42b, CD62P, and MHC class I were evaluated at 4 h of interaction with dengue virus serotype 2 (DENV-2), finding that DENV-2 induced a sharp rise in the membrane expression of all these molecules. At 2 and 4 h of DENV-2 stimulation of platelets, a significantly greater secretion of soluble CD40L (sCD40L) was found (versus basal levels) as well as cytokines such as GM-CSF, IL-6, IL-8, IL-10, and TNF-α. Compared to basal, DENV-2 elicited more than two-fold increase in these cytokines. Compared to the thrombin-induced response, the level generated by DENV-2 was much higher for GM-CSF, IL-6, and TNF-α. All these events induced by DENV end up in conspicuous morphological changes observed in platelets by confocal microscopy and transmission electron microscopy, very different from those elicited by thrombin in a more physiological scenery.

The alarming worldwide emergence of the chikungunya virus began in the last decade. Since the first autochthonous transmission in Mexico in November of 2014, the virus has spread throughout the country, resulted in multiple outbreaks. This virus produces an acute and self-limiting disease characterized by fever, polyarthralgia, myalgia, exanthema, and general malaise. It is transmitted to humans by the bite of Aedes aegypti and A. albopictus mosquitoes. The fact that the clinical presentation is similar to that produced by other arboviruses complicates its clinical diagnosis. The chronic stage of the disease can cause severe consequences lasting months or years, from local arthralgia to rheumatoid arthritis. In this review, we emphasize the public health threat posed by this highly disabling emerging disease, the clinical outcomes, and its possible physiopathological process. We outline the diagnosis and the impact that this virus has had in Mexico since its introduction.

Nucleotide-binding domain (NBD) leucine-rich repeat (LRR)-containing receptors or NLRs are a family of receptors that detect both, molecules associated to pathogens and alarmins, and are located mainly in the cytoplasm. NOD2 belongs to the NLR family and is a dynamic receptor capable of interacting with multiple proteins and modulate immune responses in a stimuli-dependent manner. The experimental evidence shows that interaction between NOD2 structural domains and the effector proteins shape the overall response against bacterial or viral infections. Other reports have focused on the importance of NOD2 not only in infection but also in maintaining tissue homeostasis. However, not only protein interactions relate to function but also certain polymorphisms in the gene that encodes NOD2 have been associated with inflammatory diseases, such as Crohn's disease. Here, we review the importance and general characteristics of NOD2, discussing its participation in infections caused by bacteria and viruses as well as its interaction with other pathogen recognition receptors or effectors to induce antibacterial and antiviral responses. Finally, the role of NOD2 in chronic inflammatory conditions and its potential to be targeted therapeutically are examined.

Alterations in the interplay between the nucleus and the cell cycle during cancer development lead to a state of genomic instability, often accompanied by observable morphologic aberrations. Tumor cells can regulate these aberrations to evade cell death, either by preventing or eliminating genomic instability. In epithelial ovarian cancer, overexpression of claudin-4 significantly contributes to therapy resistance through mechanisms associated with genomic instability regulation. However, the molecular mechanisms underlying claudin-4 overexpression in epithelial ovarian cancer remain poorly understood. In this study, we modified claudin-4 expression and employed a unique claudin mimic peptide to investigate claudin-4’s function. Our findings show that claudin-4 supports ovarian cancer cell survival by stabilizing the genome through nuclear and cell-cycle remodeling. Specifically, claudin-4 induced nuclear constriction by excluding lamin B1 and promoting perinuclear F-actin accumulation, thereby altering nuclear structure and dynamics. Similarly, cell-cycle modifications due to claudin-4 overexpression resulted in fewer cells entering the S-phase and reduced genomic instability in tumors. Importantly, disrupting claudin-4’s biological effects using claudin mimic peptide and forskolin increased the efficacy of PARP inhibitor treatment, correlating with alterations in the oxidative stress response. Our data indicate that claudin-4 protects tumor genome integrity by modulating the crosstalk between the nucleus and the cell cycle, leading to resistance to genomic instability formation and the effects of genomic instability–inducing agents. Significance: High-grade serous ovarian carcinoma is marked by chromosomal instability, which can serve to promote disease progression and allow cancer to evade therapeutic insults. The report highlights the role of claudin-4 in regulating genomic instability and proposes a novel therapeutic approach to exploit claudin-4–mediated regulation.

Most flaviviruses are transmitted horizontally between vertebrate hosts by haematophagous arthropods. Others exhibit host ranges restricted to vertebrates or arthropods. Vertebrate-specific flaviviruses are commonly referred to as no-known-vector (NKV) flaviviruses and can be separated into bat- and rodent-associated NKV flaviviruses. Rio Bravo virus (RBV) is one of eight recognized bat-associated NKV (B-NKV) flaviviruses. Studies designed to identify the genetic determinants that condition the host range restriction of B-NKV flaviviruses have never been performed. To investigate whether the host range restriction occurs at the level of attachment or entry, chimeric flaviviruses were created by inserting the pre-membrane and envelope protein genes of RBV into the genetic backbones of yellow fever virus (YFV) and Zika virus (ZIKV), two mosquito-borne flaviviruses associated with human disease. The chimeric viruses infected both vertebrate and mosquito cells. In vertebrate cells, all viruses produced similar mean peak titres, but the chimeric viruses grew more slowly than their parental viruses during early infection. In mosquito cells, the chimeric virus of YFV and RBV grew more slowly than YFV at early post-inoculation time points, but reached a similar mean peak titre. In contrast, the chimeric virus of ZIKV and RBV produced a mean peak titre that was approximately 10-fold lower than ZIKV. The chimeric virus of YFV and RBV produced an intermediate plaque phenotype, while the chimeric virus of ZIKV and RBV produced smaller plaques than both parental viruses. To conclude, we provide evidence that the structural glycoproteins of RBV permit entry into both mosquito and vertebrate cells, indicating that the host range restriction of B-NKV flaviviruses is mediated by a post-attachment/entry event.

: We provide evidence of concurrent and close sequential infections between SARS-CoV-2 and select arboviruses—namely, chikungunya virus (CHIKV); dengue viruses 1, 2, and 3 (DENV1–3), and Zika virus (ZIKV)—in patients in Guerrero, southwest Mexico, in 2020–2021. The study population consisted of 176 febrile patients with laboratory evidence of SARS-CoV-2 infection. Sera from all patients were serologically and antigenically tested for seven arboviruses known to occur in Guerrero. Eighteen patients contained CHIKV IgM, six of whom also contained CHIKV RNA. Another 16 patients contained flavivirus antigen. The flaviviruses responsible for the infections were identified by plaque reduction neutralization test as DENV1 (two patients), DENV2 (five patients), DENV3 (three patients), ZIKV (three patients), and an undetermined flavivirus (three patients). In summary, we identified patients in Guerrero, Mexico, with concurrent or recent sequential infections between SARS-CoV-2 and select arboviruses, exemplifying the importance of performing differential diagnosis in regions where these viruses cocirculate.