Frequency evaluation and molecular characterization of HHV-6 and HHV-7 among children under 5 years with fever and skin rash.

Skin rash is one of the most common complications during childhood. Viral agents play an essential role in the development of such symptoms. Present study aims to determine the prevalence and genetic variability of Human Herpesvirus 6 and 7 (HHV-6 and HHV-7) infections and their subtypes in children under 5 years of age with skin rash and negative for rubella and measles. We used serum and throat swap samples from 196 children with skin rash and fever. ELISA and IFA tests were performed to detect antibodies against HHV6/7. Sequencing was performed using Sanger sequencing, and BioEdit and MEGA10 software were used for sequence analysis. According to the results, 66% and 40% of cases were positive for HHV-6 IgM and HHV-7 IgM, respectively. According to the molecular analysis, HHV-6 Nested-PCR was positive in 18% of cases, however, HHV-7 Nested-PCR was positive in 7.7% of cases. On the other hand, HHV-6 IgG and HHV-7 IgG were positive in 91% and 55% of study cases, respectively. For HHV-6, we found some genetic variabilities resulting in antigenic changes compared to reference strains. HHV-7 isolates showed no genetic differentiation and had a stable gene sequence. Based on the results, the detection of some cases of HHV6/7 primary infection and the presence of specific symptoms of roseola in the study population needs continuous evaluation of HHV6/7 frequency and distribution, also genetic variabilities of HHV6. This can pave the way for investigating HHV6 immune evasion and vaccine research and studying the relationship between viral genetic variations and other factors like disease severity. Furthermore, it is necessary to determine the relation between HHV6 genetic changes and latent infection to be considered in possible future vaccines and antiviral drug development.

Oncolytic virus delivery modulated immune responses toward cancer therapy: Challenges and perspectives.

Oncolytic viruses (OVs) harness the hallmarks of tumor cells and cancer-related immune responses for the lysis of malignant cells, modulation of the tumor microenvironment, and exertion of vaccine-like activities. However, efficient clinical exploitation of these potent therapeutic modules requires their systematic administration, especially against metastatic and solid tumors. Therefore, developing methods for shielding a virus from the neutralizing environment of the bloodstream while departing toward tumor sites is a must. This paper reports the latest advancements in the employment of chemical and biological compounds aimed at safe and efficient delivery of OVs to target tissues or tumor deposits within the host.

Prevalence and genotypic characterization of human parvovirus B19 in hemophilia patients.

Background and Objectives: Parvovirus B19 (B19V) is usually transmitted through respiratory tract, but can also be received through blood transfusion. This study evaluated the seroprevalence, DNA existence, and circulating genotypes of B19V in hemophilia patients. Materials and Methods: Serum samples of cases and controls were analyzed for B19V using ELISA and real-time PCR. Finally, obtained sequences were used for genotyping. Results: Among cases, 3% were anti-B19V IgM positive and 47% were anti-B19V IgG positive and B19V DNA was detected in 16% of them. However, among controls, 38% were anti-B19V IgG positive (P>0.05) and 5% were B19V DNA positive (P= 0.019). Also ∼13% of cases were positive and all of controls were negative for IgG avidity test (P= 0.029). Viral load in case group was higher than control group (P = 0.037). Conclusion: Since hemophilia patients receive large amounts of blood factors, prevalence of B19V in these patients might be higher than normal subjects.

Immunopathology and Immunopathogenesis of COVID-19, what we know and what we should learn.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) directly interacts with host's epithelial and immune cells, leading to inflammatory response induction, which is considered the hallmark of infection. The host immune system is programmed to facilitate the clearance of viral infection by establishing a modulated response. However, SARS-CoV-2 takes the initiative and its various structural and non-structural proteins directly or indirectly stimulate the uncontrolled activation of injurious inflammatory pathways through interaction with innate immune system mediators. Upregulation of cell-signaling pathways such as mitogen-activate protein kinase (MAPK) in response to recognition of SARS-CoV-2 antigens by innate immune system receptors mediates unbridled production of proinflammatory cytokines and cells causing cytokine storm, tissue damage, increased pulmonary edema, acute respiratory distress syndrome (ARDS), and mortality. Moreover, this acute inflammatory state hinders the immunomodulatory effect of T helper cells and timely response of CD4+ and CD8+ T cells against infection. Furthermore, inflammation-induced overproduction of Th17 cells can downregulate the antiviral response of Th1 and Th2 cells. In fact, the improperly severe response of the innate immune system is the key to conversion from a non-severe to severe disease state and needs to be investigated more deeply. The virus can also modulate the protective immune responses by developing immune evasion mechanisms, and thereby provide a more stable niche. Overall, combination of detrimental immunostimulatory and immunomodulatory properties of both the SARS-CoV-2 and immune cells does complicate the immune interplay. Thorough understanding of immunopathogenic basis of immune responses against SARS-CoV-2 has led to developing several advanced vaccines and immune-based therapeutics and should be expanded more rapidly. In this review, we tried to delineate the immunopathogenesis of SARS-CoV-2 in humans and to provide insight into more effective therapeutic and prophylactic strategies.

Role of myeloid-derived suppressor cells in viral respiratory infections; Hints for discovering therapeutic targets for COVID-19.

The expansion of myeloid-derived suppressor cells (MDSCs), known as heterogeneous population of immature myeloid cells, is enhanced during several pathological conditions such as inflammatory or viral respiratory infections. It seems that the way MDSCs behave in infection depends on the type and the virulence mechanisms of the invader pathogen, the disease stage, and the infection-related pathology. Increasing evidence showing that in correlation with the severity of the disease, MDSCs are accumulated in COVID-19 patients, in particular in those at severe stages of the disease or ICU patients, contributing to pathogenesis of SARS-CoV2 infection. Based on the involved subsets, MDSCs delay the clearance of the virus through inhibiting T-cell proliferation and responses by employing various mechanisms such as inducing the secretion of anti-inflammatory cytokines, inducible nitric oxide synthase (iNOS)-mediated hampering of IFN-γ production, or forcing arginine shortage. While the immunosuppressive characteristic of MDSCs may help to preserve the tissue homeostasis and prevent hyperinflammation at early stages of the infection, hampering of efficient immune responses proved to exert significant pathogenic effects on severe forms of COVID-19, suggesting the targeting of MDSCs as a potential intervention to reactivate T-cell immunity and thereby prevent the infection from developing into severe stages of the disease. This review tried to compile evidence on the roles of different subsets of MDSCs during viral respiratory infections, which is far from being totally understood, and introduce the promising potential of MDSCs for developing novel diagnostic and therapeutic approaches, especially against COVID-19 disease.

Correction to: Virotheranostics, a double-barreled viral gun pointed toward cancer; ready to shoot?

[This corrects the article DOI: 10.1186/s12935-020-01219-6.].

Virotheranostics, a double-barreled viral gun pointed toward cancer; ready to shoot?

Compared with conventional cancer treatments, the main advantage of oncolytic virotherapy is its tumor-selective replication followed by the destruction of malignant cells without damaging healthy cells. Accordingly, this kind of biological therapy can potentially be used as a promising approach in the field of cancer management. Given the failure of traditional monitoring strategies (such as immunohistochemical analysis (in providing sufficient safety and efficacy necessary for virotherapy and continual pharmacologic monitoring to track pharmacokinetics in real-time, the development of alternative strategies for ongoing monitoring of oncolytic treatment in a live animal model seems inevitable. Three-dimensional molecular imaging methods have recently been considered as an attractive approach to overcome the limitations of oncolytic therapy. These noninvasive visualization systems provide real-time follow-up of viral progression within the cancer tissue by the ability of engineered oncolytic viruses (OVs) to encode reporter transgenes based on recombinant technology. Human sodium/iodide symporter (hNIS) is considered as one of the most prevalent nuclear imaging reporter transgenes that provides precise information regarding the kinetics of gene expression, viral biodistribution, toxicity, and therapeutic outcomes using the accumulation of radiotracers at the site of transgene expression. Here, we provide an overview of pre-clinical and clinical applications of hNIS-based molecular imaging to evaluate virotherapy efficacy. Moreover, we describe different types of reporter genes and their potency in the clinical trials.

Metabolic host response and therapeutic approaches to influenza infection.

Based on available metabolomic studies, influenza infection affects a variety of cellular metabolic pathways to ensure an optimal environment for its replication and production of viral particles. Following infection, glucose uptake and aerobic glycolysis increase in infected cells continually, which results in higher glucose consumption. The pentose phosphate shunt, as another glucose-consuming pathway, is enhanced by influenza infection to help produce more nucleotides, especially ATP. Regarding lipid species, following infection, levels of triglycerides, phospholipids, and several lipid derivatives undergo perturbations, some of which are associated with inflammatory responses. Also, mitochondrial fatty acid ß-oxidation decreases significantly simultaneously with an increase in biosynthesis of fatty acids and membrane lipids. Moreover, essential amino acids are demonstrated to decline in infected tissues due to the production of large amounts of viral and cellular proteins. Immune responses against influenza infection, on the other hand, could significantly affect metabolic pathways. Mainly, interferon (IFN) production following viral infection affects cell function via alteration in amino acid synthesis, membrane composition, and lipid metabolism. Understanding metabolic alterations required for influenza virus replication has revealed novel therapeutic methods based on targeted inhibition of these cellular metabolic pathways.

Induction of protective immune response to intranasal administration of influenza virus-like particles in a mouse model.

Human influenza A viruses (IAVs) cause global pandemics and epidemics, which remains a nonignorable serious concern for public health worldwide. To combat the surge of viral outbreaks, new treatments are urgently needed. Here, we design a new vaccine based on virus-like particles (VLPs) and show how intranasal administration of this vaccine triggers protective immunity, which can be exploited for the development of new therapies. H1N1 VLPs were produced in baculovirus vectors and were injected into BALB/c mice by the intramuscular (IM) or intranasal (IN) route. We found that there were significantly higher inflammatory cell and lymphocyte concentrations in bronchoalveolar lavage samples and the lungs of IN immunized mice; however, the IM group had little signs of inflammatory responses. On the basis of our results, immunization with H1N1 influenza VLP elicited a strong T cell immunity in BALB/c mice. Despite T cell immunity amplification after both IN and IM vaccination methods in mice, IN-induced T cell responses were significantly more intense than IM-induced responses, and this was likely related to an increased number of both CD11bhigh and CD103+ dendritic cells in mice lungs after IN administration of VLP. Furthermore, evaluation of interleukin-4 and interferon gamma cytokines along with several chemokine receptors showed that VLP vaccination via IN and IM routes leads to a greater CD4+ Th1 and Th2 response, respectively. Our findings indicated that VLPs represent a potential strategy for the development of an effective influenza vaccine; however, employing relevant routes for vaccination can be another important part of the universal influenza vaccine puzzle.

Influenza vaccine: Where are we and where do we go?

The alarming rise of morbidity and mortality caused by influenza pandemics and epidemics has drawn attention worldwide since the last few decades. This life-threatening problem necessitates the development of a safe and effective vaccine to protect against incoming pandemics. The currently available flu vaccines rely on inactivated viral particles, M2e-based vaccine, live attenuated influenza vaccine (LAIV) and virus like particle (VLP). While inactivated vaccines can only induce systemic humoral responses, LAIV and VLP vaccines stimulate both humoral and cellular immune responses. Yet, these vaccines have limited protection against newly emerging viral strains. These strains, however, can be targeted by universal vaccines consisting of conserved viral proteins such as M2e and capable of inducing cross-reactive immune response. The lack of viral genome in VLP and M2e-based vaccines addresses safety concern associated with existing attenuated vaccines. With the emergence of new recombinant viral strains each year, additional effort towards developing improved universal vaccine is warranted. Besides various types of vaccines, microRNA and exosome-based vaccines have been emerged as new types of influenza vaccines which are associated with new and effective properties. Hence, development of a new generation of vaccines could contribute to better treatment of influenza.