Interferon-inducible protein (IFI) 16 regulates Chikungunya and Zika virus infection in human skin fibroblasts

Febrile or Exanthematous Illness Associated with Zika, Dengue, and Chikungunya Viruses, Panama.

Chikungunya virus (CHIKV) poses a significant challenge as there are currently no targeted antiviral drugs or vaccines to combat this infection. Here, we demonstrate that interferon-induced transmembrane proteins (IFITMs), including IFITM1, IFITM2, and IFITM3, which are interferon-stimulated genes (ISGs), inhibit CHIKV infection in human skin fibroblasts. Overexpression of IFITMs in cells restricts viral infection, whereas knockdown of IFITMs enhances viral infection. IFITMs overexpression causes a substantial upregulation of antiviral genes, namely TLR3, TLR7, TLR8, and TLR9, and their downstream signaling molecules such as TRADD, IRAK1, TRAF6, and MAP3K7, involved in TLRs signaling pathways. Furthermore, the DHX58 gene encoding the LGP2 protein, a negative regulator of RIG-I in RLRs signaling pathways, was downregulated in the overexpressed cells. Transcription factors including interferon regulatory factors (IRF) 3/5/7, which are downstream signaling components of both TLR and RLR signaling pathways, were also upregulated, resulting in enhanced IFNs signaling. IFITMs not only inhibits the early and late stages of viral infection but can also alter the antiviral innate-immune response to restrict CHIKV infection in human skin fibroblasts. Additionally, IFITMs exhibit their antiviral activity against Zika virus (ZIKV). Altogether, these results show the broad-spectrum antiviral property of IFITMs against arboviruses in foreskin cells.

Risk for Emergence of Dengue and Chikungunya Virus in Israel

Yellow fever (YF), Chikungunya (CHIK), and Zika(ZIK) are among re-emerging arboviral diseases of major public health concern. Despite the proximity of the Gambella Region to South Sudan where arboviral cases have been recorded repeatedly the current epidemiological situation is unclear in this part of southwest Ethiopia. Therefore, we conducted a community-based seroprevalence survey of YF virus (YFV), CHIK virus (CHIKV), and ZIK virus (ZIKV) infections in two selected districts. A cross-sectional study was conducted in two locations of the Gambella region (Lare and Itang) to investigate the seroprevalence of these viruses’ infections. Blood samples were collected from the study participants and screened for IgG antibodies specific to YFV and CHIKV infections using enzyme-linked immunosorbent assays (ELISA). For the detection of ZIKV specific IgG antibodies, Blockade-of-binding ELISA was used. Data were analyzed using the STATA version 13.1 Softwares. A total of 150 individuals (96 males and 54 females, age ranging from 18 to 65 years, mean age ± SD = 35.92 ± 10.99) participated and provided blood samples. Among the 150 samples 135, 90, and 150 were screened for YFV, CHIKV, and ZIKV, respectively. Hence, 2.9% (95% CI: 1.1–7.7%), 15.6% (95% CI: 9.3–24.8%), and 27.3% (95% CI: 20.7–35.3%) of samples tested positive for IgG antibodies to YFV, CHIKV, and ZIKV infections, respectively. Among the individual seropositive for ZIKV, YFV and CHIKV, only six, one and three had a history of residence outside the Gambella region respectively. Agro-pastoral occupation was significantly associated with a higher prevalence of IgG against CHIKV (AOR = 14.17; 95%CI: 2.30, 87.30) and residency in the Lare district (AOR = 11; 95%CI: 3.31, 39.81) was found to be significantly associated with a higher prevalence of IgG against ZIKV. Our findings revealed the occurrence of YFV, CHIKV and ZIKV infections in the study locations.

Dengue, chikungunya, and Zika virus infections imported to Paris between 2009 and 2016: Characteristics and correlation with outbreaks in the French overseas territories of Guadeloupe and Martinique

Underdiagnosis of arbovirus infections in returned travelers in an area with growing circulation of Aedes albopictus in North-Eastern France

Atypical Chikungunya Virus Infections in Immunocompromised Patients

Amongst the arthritis-causing arboviruses, i.e. those spread by insects, the alphavirus group is of special interest. These viruses occasionally cause vast outbreaks, such as O'nyong-nyong in Africa in 1959. In Fennoscandia, Sindbis-related Ockelbo, Pogosta, or Karelian fever viruses have been found to cause significant morbidity. The major symptoms in addition to joint inflammation are fever, fatigue, headache and rash. The joint symptoms may persist for weeks, even months. The diagnosis is based on the clinical picture and serology. The causative viruses are closely related but not identical. It appears that at least in Finland the Pogosta disease is more common than thought, and the symptoms may often be overlooked. Several factors related to the viruses, their hosts, and global environmental changes may affect the spread of these viruses. All over the world arbovirus-caused diseases have increased, because of global changes.

Zika and Chikungunya Virus and Risk for Venous Thromboembolism

Being obligate parasites, viruses use various host cell machineries in effectively replicating their genome, along with virus-encoded enzymes. In order to carry out infection and pathogenesis, viruses are known to manipulate fundamental cellular processes in cells and interfere with host gene expression. Several viruses interact with the cellular proteins involved in the Wnt/β-catenin pathway; however, reports regarding the involvement of protein components of the Wnt/β-catenin pathway in Chikungunya virus (CHIKV) infection are scarce. Additionally, there are currently no remedies or vaccines available for CHIKV. This is the first study to report that modulation of the Wnt/β-catenin pathway is crucial for effective CHIKV infection. These investigations deepen the understanding of the underlying mechanisms of CHIKV infection and offer new avenue for developing effective countermeasures to efficiently manage CHIKV infection.

Molecular and serological techniques to detect co-circulation of DENV, ZIKV and CHIKV in suspected dengue-like syndrome patients

We report the molecular evidence of dengue virus (DENV) and chikungunya virus (CHIKV) infection in symptomatic individuals in Cameroon and Gabon, respectively. Arthropod-borne viruses (arboviruses) are distributed in the tropical or subtropical regions, with DENV having the highest burden. The morbidity and mortality related to arboviral diseases raise the concern of timely and efficient surveillance and care. Our aim was to assess the circulation of arboviruses [DENV, CHIKV, Zika virus (ZIKV)] among febrile patients in Dschang (West Cameroon) and Kyé-ossi (South Cameroon, border with Gabon and Equatorial Guinea). Dried blood spots were collected from 601 consenting febrile patients, and 194 Plasmodium spp.-negative samples were tested for the molecular detection of cases of DENV, CHIKV and ZIKV infection. Overall, no case of ZIKV infection was found, whereas one case of DENV infection and one case of CHIKV infection were detected in Dschang and Kyé-ossi, respectively, with the CHIKV-infected patient being resident in Gabon. Our findings suggest the need to establish an active surveillance of arbovirus transmission in Cameroon and bordering countries.

Establishment of a viral infection in the host involves complex interactions between the virus and the host. The present study was undertaken to evaluate one such interaction between a host microRNA (miRNA) with both the virus and its cellular target. Through a comprehensive high-throughput screen of a human miRNA mimics library, we identified that hsa-miR-122b-5p bound to chikungunya virus (CHIKV) 3'-untranslated region (3'-UTR), which we abrogated upon mutating the binding sites of the miRNA and determined that this miRNA regulated CHIKV infection. In-depth scrutiny of this miRNA's expression in CHIKV-susceptible host cells divulged that it was mainly expressed in macrophages, and temporal expression profiling analysis in these cells revealed that its expression negatively correlated to the virus infection. We further identified cellular targets of miR-122b-5p through global RNA seq analysis using antagomiRs, among which histone deacetylase 4 (HDAC4) displayed attributes that promoted CHIKV infection in macrophages. To dissect this phenomenon further, we performed loss-of-function assays using both miR-122b-5p and HDAC4 and observed regulation of pro-inflammatory cytokines, including the type I interferon system. Furthermore, miRNA mimics and antagomiR assays indicated that regulation of HDAC4 by miR-122b-5p may be associated with changes in the nuclear translocation of phosphorylated IRF3 during CHIKV infection. While this suggests a possible link, additional studies are needed to confirm this interaction and its underlying mechanism. Taken altogether, our study provides insights into the dual regulatory function of miR-122b-5p during CHIKV infection, highlighting its capacity to decrease viral titer by binding directly to the 3'UTR of the viral genome and its potential to promote nuclear translocation of phosphorylated IRF3, which may be indirectly influenced by modulation of its cellular target, HDAC4, thereby regulating host immune responses during CHIKV infection in macrophages. These findings may have significant implications for understanding the pathogenesis of CHIKV and for developing novel therapeutic strategies.IMPORTANCEHuman microRNAs (miRNAs) are central regulators of viral infection, acting through direct targeting of viral genomes or by modulating host cellular pathways. In this study, we demonstrate that miR-122b-5p plays a dual antiviral role during chikungunya virus (CHIKV) infection in macrophages-critical immune cells that serve as viral reservoirs. We show that miR-122b-5p directly binds to the 3' untranslated region of the CHIKV genome, thereby suppressing viral replication. Additionally, we uncover a previously uncharacterized mechanism in which miR-122b-5p modulates the host innate immune response by repressing HDAC4, a negative regulator of the type I interferon pathway. This repression may influence nuclear translocation of phosphorylated IRF3, potentially enhancing the antiviral transcriptional response. Our findings not only deepen our understanding of macrophage-intrinsic antiviral defenses against CHIKV but also highlight miR-122b-5p as a potential therapeutic target for enhancing host immunity and limiting viral propagation.

Chikungunya virus: An emerging public health challenge for Pakistan

Limited information is available on the seroprevalence of chikungunya virus (CHIKV) infection and maternal-fetal transmission incidence of CHIKV and dengue virus (DENV) infections during the 2008-2009 CHIKV outbreak in southern Thailand. A community-based post-epidemic seroprevalence study was conducted in parturient women admitted to the Thepa District Hospital in Songkhla Province, Thailand, for delivery from November 2009 to May 2010. The women were tested for chikungunya (CHIK) IgM/IgG and dengue (DEN) IgM/IgG. Cord blood samples were also tested for CHIK IgM or DEN IgM in women who tested positive for CHIK IgM or DEN IgM, respectively. The seroprevalence of CHIKV infection (CHIK IgM or IgG positive) was 227/319 (71·2%) with pre-outbreak seroprevalence (IgM-/IgG+) of 43·6% and the seroprevalence of DENV infection was 288/319 (90·3%). Complications during pregnancy, newborn outcomes and congenital anomalies were not different in those who had recent, remote or no CHIKV infections. None of the newborns whose mothers were CHIK or DEN IgM positive had cord blood positive for both CHIK and DEN IgM. In conclusion, both CHIKV and DENV are endemic in southern Thailand; during the recent CHIKV outbreak CHIK seroprevalence increased from 43·6% to 71·2%.