The AP-1 pathway; A key regulator of cellular transformation modulated by oncogenic viruses.

Cancer progression is critically associated with modulation of host cell signaling pathways. Activator protein-1 (AP-1) signaling is one such pathway whose deregulation renders the host more susceptible to cancer development. Oncogenic viruses, including hepatitis B virus, hepatitis C virus, human papilloma virus, Epstein-Barr virus, human T-cell lymphotropic virus type 1, and Kaposi's sarcoma-associated herpes virus, are common causes of cancer. This review discusses how these oncoviruses by acting through various aspects of the host cell signaling machinery such as the AP-1 pathway might affect oncoviral tumorigenesis, replication, and pathogenesis. The review also briefly considers how the pathway might be targeted during infections with these oncogenic viruses.

Investigation of SARS CoV-2 virus in environmental surface.

The prevalent respiratory viruses such as SARS-CoV-2 probably persist for a long time on fomites and environmental surfaces. Some recent studies have detected SARS-CoV-2 RNA on the surface of cell phones, door handles and other items in the inhabited sites of confirmed cases. For the aim of this study, a total of 50 environmental surface samples of SARS-CoV-2 was collected from Imam Khomeini Hospital in Ardabil. Forty-one environmental surface samples were proved negative for SARS-CoV-2 RNA while nine surface samples were positive. Our findings regarding surfaces contaminated with the virus are consistent with the results of recent similar researches as it was revealed that a number of different samples taken from hospital surfaces such as handles, cupboards, light switches, and door handles were positive for the presence of SARS-Cov-2.

Evaluation of masks' internal and external surfaces used by health care workers and patients in coronavirus-2 (SARS-CoV-2) wards.

One of the simplest and most effective individual measures is to wear a mask to prevent the spread of respiratory droplets from carriers to healthy people and patients admitted to corona wards and their staff. This research aimed to investigate the contamination of internal and external surfaces of various masks used by patients and staff with SARS coronavirus, as well as the possibility of airborne transmission in Imam Khomeini Hospital, Ardabil. For this purpose, twenty-five staff members and ten patients participated voluntarily in this cross-sectional study. Sampling was performed using swaps on both sides (inside and outside) of various surgical masks, N-95, and filtering face piece FFP2 through standard methods in compliance with the relevant conditions and from a surface of at least 5 cm2. Next, the collected samples were immediately transferred to a laboratory and analyzed by real-time PCR method to detect the presence of SARS-CoV-2 virus after viral genome extraction. Based on the obtained results, from a total of 30 collected samples (25 of personnel masks plus 5 samples of hospitalized patients' masks). A total of 60 masks were sampled. For every collected sample, the researchers studied both inside and outside of the mask. Upon analyzing the data, it was showed that 6 mask samples were positive for the presence of coronavirus. Nonetheless, all samples taken from both inside and outside of the personnel masks (N-95 and FFP2 types of masks) were negative. Among the 6 positive samples, four cases were related to the internal part, one case to the outer part of the three-layer surgical masks, and one to the outer part of the N-95 masks in hospitalized patients. As masks reduce the concentration of virus particles, they can play an important role in creating immunity.

The healthy behaviours and COVID-19 mortality among Iranian women: a case-control study.

BACKGROUND: Women are among the susceptible groups to Coronavirus disease-19 (COVID-19) in Ardabil, north-west of Iran, despite the current global status. The underlying causes of high incidence and fatality rate of women in Ardabil are not fully understood. Hence, this study aimed to investigate the healthy behaviours in women of Ardabil and its relationship with COVID-19 mortality. METHODS: We conducted a case-control study to compare the adherence to health protocols and behaviours with respect to COVID-19 between the infected (261 patients) and healthy (515 persons) women. Health protocols and behaviours such as using mask, gloves, disinfectants, history of travelling and contacting, and attending various gatherings and places during the COVID-19 pandemic along with demographic variables were defined as independent variables, and COVID-19 death rate was defined as the dependent variable. Multivariable logistic regression methods were used to explore the risk factors associated with COVID-19 mortality. RESULTS: Chi-square and Fisher tests showed significant differences between infected and healthy women in terms of history of contact and traveling (p < 0.05), wearing mask (p < 0.001), going to work place (p < 0.001), and attend public gatherings (p = 0.038). Multivariable logistic regression disclosed that the age group over 80 years: 8.97 times (95% CI 2.27-29.85), women with underlying chronic diseases: 4.14 times (95% CI 1.61-10.64), and obese women: 3.01 times (95% CI 1.04-6.03) were more likely to die from COVID-19 than other women. CONCLUSION: Considering the high incidence and mortality rate in Ardabil women due to COVID-19 and the corresponding health behavioural factors, special emphasis should be given to the increase of women awareness on the importance of healthy behaviours, diet, and life-style.

Multi-epitope vaccine against SARS-CoV-2 targeting the spike RBD: an immunoinformatics approach.

Aim: We designed a SARS-CoV-2 epitope vaccine based on the receptor-binding domain (RBD) in virus spike protein. Methods: RT-PCR performed on nasopharyngeal swab COVID-19 patients. After registering RBD region in the GenBank, physicochemical parameters, secondary structure, homology modeling, 3D structure of RBD region and antigenicity were determined using ProtParam ExPASy, PSIPRED, MolProbity, IEDB and Vaxijen online tools, respectively. Results: B and T cell epitopes were predicted in terms of non-allergenicity and antigenicity. MolProbity analysis provided a qualitative model for RBD. The homology model showed that most of the residues are in optimal district of energy. Conclusion: High immunogenicity score of epitopes indicates promising candidates for the development of multi-epitope vaccines. It may help to develop an effective vaccine.

In order to identify the sequence of RBD region of S protein in SARS-CoV-2, RT-PCR test was performed on nasopharyngeal swab samples of four COVID-19 patients referred to Imam Khomeini Hospital in Ardabil. After registering the sequence of the RBD region in the GenBank database, the physicochemical parameters, secondary structure, homology modeling, 3D structure of the RBD region and antigenicity were determined using ProtParam ExPASy, PSIPRED, MolProbity, IEDB and Vaxijen online tools, respectively.

Investigating SARS-CoV-2 RNA in five municipal wastewater treatment plants, hospital wastewater and wastewater collection networks during the COVID-19 pandemic in Ardabil Province, Iran.

Since 2019, the outbreak of coronavirus with acute respiratory symptoms has caused an epidemic worldwide. Transmission of the disease through respiratory droplets was announced as the main mode of transmission in 2020. But in this study, we discussed the method of indirect transmission of the virus through sewage. In this study, effluents related to urban and hospital wastewater treatment plants in 5 regions of Ardabil Province (northwest of Iran) were investigated. In this research, 120 samples were kept in pre-test conditions (temperature -20 degrees Celsius). To identify the viral genome, special primer and chain reaction probe targeting ORF1ab and N (nucleoprotein gene) genes were used. Out of a total of 120 samples, a total of 3 samples were positive. Wastewater epidemiology (WBE) can be considered as a cost-effective method in the diagnosis and prediction of pathogenic agents. And be considered an effective method for decision-making in order to protect the health of citizens.

The mutations frequency of enhancer II/HBx regions of hepatitis B virus in acutely infected Iranian patients: a cross-sectional study.

Background and Objectives: The viral transactivator HBx protein affect cellular, viral and pregenomic factors pathway. Mutations in this protein can produce new viruses with new antigenic determinants that are generally related to developing cancerous. Materials and Methods: In this cross-sectional study, 33 serum samples of patients diagnosed with acute HBV infection were investigated for HBeAg and HBV DNA viral load and HBx gene mutations. mutation in the HBx protein detected by sequencing analysis. Results: Out of the 33 samples, 19 samples were males (57.6%), and 14 samples were females. 15 (45.5%) were positive for HBx DNA and 18 patients were negative for HBx DNA (54.5%). After sequencing, three mutations were recognized in HBx at nucleotide positions 147, 148, and 391 that were stationed to G1524A, G1525A, and G1767C mutations. Conclusion: The analysis result of this study shows G1524A and G1525A mutations that an important role in altering the inhibition function of the HBx activity domain. The G1767C mutation inactivates HBx transactivation activity. These mutations have a critical role in the pathogenicity of the virus, and the intensity of hepatic tissue demolition and the development of cirrhosis or carcinoma in patients can be understood.

SARS-CoV-2 in municipal wastewater treatment plant, collection network, and hospital wastewater.

The current outbreak of coronavirus disease (COVID-19) has led to creating a public health emergency conditions since 2019. COVID-19, which is caused by SARS-CoV-2, is spread via human-to-human transmission by direct contact or droplets. Through conducting this study, we were looking for detecting SARS-CoV-2 in wastewater produced in Iran country (Ardabil, Nir, Khalkhal, and Kowsar) (wastewater collection network, wastewater treatment plant, and hospital wastewater). In this research, samples (n=76) were collected from influent and effluent of municipal and hospital wastewater treatment plants, and some samples were also collected from Ardabil municipal wastewater manholes. The sampling duration included the white (lower risk of COVID-19) and red (high risk of COVID-19) conditions. Samples were stored at -20 °C for further diagnostic tests. The specific primer and probe real-time reverse transcriptase-polymerase chain reaction (real-time PCR) targeting ORF1ab and N genes (nucleoprotein gene) were applied to detect viral genomes of the SARS-CoV-2 virus in the wastewater samples. Out of 76 samples, a total of 15 samples (19.73%) collected from wastewater in Ardabil province (Ardabil, Nir, Khalkhal, and Kowsar), were positive in terms of SARS-CoV-2. Wastewater epidemiology can facilitate detection of the incidence of pathogens through metropolises, measurement of population prevalence without direct testing, and provision of information to the public health system about the efficiency of intervening efforts. Graphical abstract.

Evolution and diversity of human adenoviruses isolated from patients with keratoconjunctivitis.

Background and Objectives: Human adenovirus type 8 is a highly contagious eye disease and is considered as the most common epidemic keratoconjunctivitis worldwide. The virus may alter the course of detection as mutations and recombination in surface antigens are associated with binding and pathogenesis in human adenovirus. The recognition of new recombinant human adenovirus has been based on sequencing of three genes, penton base, hexon and fiber. Materials and Methods: 50 suspected samples of ocular keratoconjunctivitis were selected over 6 months. Following DNA extraction from isolates positive for cytopathic effect in each well, the complete sequences of hexon, fiber, and penton regions were performed on the genome of human adenovirus isolates using PCR. The sequences of capsid genes, including hexon, fiber, and penton were assessed to observe the evidence of recombination at the molecular level using genetic tools. Results: The results of nucleotide and amino acid sequence of 5/50 patients with epidemic keratoconjunctivitis positive for hypervariable region of hexon (132aa -449), hypervariable of knob fiber (183aa -362) and hypervariable penton (106aa -466) isolates showed nucleotide and amino acid identity of 98% and 99.41%, 99% and 100%, 95% and 99.72% with hexon, fiber and penton of human adenovirus 8 subtypes. The results of phylogenetic tree and Simplot of the entire sequences and hypervariable regions of isolated hexon, fiber and penton showed all the isolates of human adenovirus from Ahvaz, Iran, were clustered with human adenovirus 8A, B, E, P and J, subtypes isolated strains from different regions of the world. Conclusion: The results of this study revealed that the human adenovirus isolates from patients with epidemic keratoconjunctivitis were closed to human adenovirus 8A, B, E, P and J subtypes. To determine the emergence of new human adenovirus D8 subtypes strain, analysis of complete genome sequence of human adenovirus was required.

Identification coronavirus (SARS-CoV-2) and physicochemical qualities in various water sources and the efficiency of water treatment plants in their removal- case study: Northwest region of Iran.

The presence of SARS-CoV-2 virus in water resources and the transmission of diseases caused by it is one of the factors threatening the quality of water resources. This study for the first time concentrates on the presence of SARS-CoV-2 in water resources an urban location. In the present study, the samples were collected from known depth (30-50 cm) of rivers, dams and lakes. In each sample of water collected, different parameters such as residual chlorine, pH (phenol red), turbidity, total dissolved solids and temperature were also measured. Out of 267 samples, two samples were detected to be positive which their Ct values were 34.2 and 35.67. The existence of viable form of this virus in water and wastewater may be associated with issues for providing public health and difficulties in implementation of pandemic control strategies, and this situation can be exacerbated in developing countries that do not have adequate access to sanitation and safe water.

SARS-CoV-2 in domestic cats (Felis catus) in the northwest of Iran: Evidence for SARS-CoV-2 circulating between human and cats.

This study aimed to investigate the prevalence of COVID-19 in domestic cats, focusing on the disease in the northwest of Iran and then showing the natural transmission of SARS-COV-2 circulating between domestic cats and humans. After receiving ethic codes from Tehran University of Medical Sciences (IR.TUMS.VCR.REC.1399.303) and confirmed by the Center of Communicable Diseases Control (CDC) of Iran, 124 domestic cats were collected from the homes and only one hospital of Meshkin -Shahr district from northwestern Iran where SARS-CoV-2 patients were hospitalized and quarantined during 2020. Samples were prepared from fluid materials of oropharynx and nasopharynx. All samples were tested by real-time PCR (RT-PCR) using specific genes N and ORF1ab in Pasteur Institute of Iran, and then partial sequence analyses of S gene were performed. All collected cats were kept in separated cages until SARS-COV-2 infection was confirmed with the RT-PCR. RT- PCR Ct values of 123 collected cats were ≥40; thus, all of them showed negative results, but one of the collected cats with close contact with its owner, whom confirmed SARS-CoV-2 showed positive results with gene N(Ct=30) and gene ORF1ab (Ct=32). Furthermore, the positive pet cat showed respiratory and gastro-intestinal clinical manifestations, and its owner was infected with SARS-CoV-2 two weeks ago. Cats are susceptible animals to SARS-CoV-2 infection. Epidemiological evidence showed that SARS-COV-2 is able to transmit to healthy cats due to having close contact with its owner as a reverse zoonosis.

The immune response and immune evasion characteristics in SARS-CoV, MERS-CoV, and SARS-CoV-2: Vaccine design strategies.

The worldwide outbreak of SARS-CoV-2, severe acute respiratory syndrome coronavirus 2 as a novel human coronavirus, was the worrying news at the beginning of 2020. Since its emergence complicated more than 870,000 individuals and led to more than 43,000 deaths worldwide. Considering to the potential threat of a pandemic and transmission severity of it, there is an urgent need to evaluate and realize this new virus's structure and behavior and the immunopathology of this disease to find potential therapeutic protocols and to design and develop effective vaccines. This disease is able to agitate the response of the immune system in the infected patients, so ARDS, as a common consequence of immunopathological events for infections with Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV, and SARS-CoV-2, could be the main reason for death. Here, we summarized the immune response and immune evasion characteristics in SARS-CoV, MERS-CoV, and SARS-CoV-2 and therapeutic and prophylactic strategies with a focus on vaccine development and its challenges.

Parechovirus and enteroviruses among young infants with sepsis in Iran.

BACKGROUND AND OBJECTIVES: Human parechoviruses (HPeV) and Human enteroviruses (EV) frequently cause a sepsis-like illness in young infants (younger than three months). Therefore, this study was conducted to determine the frequency of HPeV and EV among the young infants with clinical signs and symptoms of sepsis in Ahvaz city, Iran. MATERIALS AND METHODS: The blood specimens were collected from 100 (younger than 90 days hospitalized infants) including 54 (56.25%) males and 46 (43.75%) females with clinical signs and symptoms of sepsis-like disease. The RNA was extracted and tested for detection of VP1 region of HPeV and 5 UTR (Untranslated Region) of EV by RT-PCR. The sequences of positive of HPeV were further analyzed to determine HPeV genotyping. RESULTS: 5/100 (5%) of patients including 2/46 (2%) females and 3/54 (3%) males tested positive for HPeV (P=0.85). The analysis of 5 positive VP1 region of HPeV revealed the genotype 1. The analysis of sequencing and phylogenetic tree revealed that the isolated HPeVs were genotype 1. While 38/100 (38%) specimens including 16 (16%) females and 22 (22%) males were tested positive for EV (P=0.68). CONCLUSION: The frequency of HPeV genotype 1 was 5% among the young infants with sepsis. While frequency of EV was 38% among the young infants with sepsis. This study showed HPeV genotype 1 and EV are dominant in this region.

A systematic review of emerging human coronavirus (SARS-CoV-2) outbreak: focus on disinfection methods, environmental survival, and control and prevention strategies.

Recently, an outbreak of a novel human coronavirus which is referred to as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (COVID-19) by the World Health Organization (WHO) was identified in Wuhan, China. To help combat the pandemic, a systematic review (SR) was performed to collect all available studies concerning inactivation methods, environmental survival, and control and prevention strategies. A comprehensive literature survey yielded 42 eligible studies which included in the SR. The results confirmed that the WHO recommended two alcohol-based hand rub formulations (ethanol 70-95% and 2-propanol 70-100%) had an efficient virucidal activity in less than 60 s by more and equal 4 log10 (≥ 99.99) approximately and could be used for disinfection in public health and health-care facilities. The findings indicated that SARS-CoV-1 and SARS-CoV-2 can survive under different environmental conditions between 4 and 72 h approximately. The results also demonstrate that temperature and relative humidity are important factors in the survival of SARS-CoV-2. The main strategies recommended by the WHO to avoid contracting SARS-CoV-2 are hand washing several times in the day and maintaining social distancing with others. It is important to note that the more studies require addressing, the more possible airborne transmission due to the survival of SARS-CoV-2 in aerosols for 3 h approximately. We hope that the results of the present SR can help researchers, health decision-makers, policy-makers, and people for understanding and taking the proper behavior to control and prevent further spread of SARS-CoV-2.

Investigation of SARS-CoV-2 virus on nozzle surfaces of fuel supply stations in North West of Iran.

There are several ways for transmitting the SARS-CoV-2 virus to humans, and one of these ways is the contact with infected surfaces. Fuel stations have been a major concern for people and health experts due to the frequent use of common nozzles. This study was performed to identify the COVID-19 virus in the nozzles of fuel supply stations. In the current research, 25 fuel supply stations along the main street ways were investigated to recognize Coronavirus infection on the surfaces of the nozzles. For each fuel supply station, 4 nozzles were chosen (a total of 100 samples). The sampling was carried out at two periods of time, that is, before and after quarantine restrictions. Swapping was used for surface sampling, and Real-time PCR was used to determine the positive and negative results. The results showed that out of nine fuel supply stations (36 samples of nozzle surfaces), five were positive for the presence of SARS-CoV-2 on the nozzle surfaces before the corona restriction. The results showed that in the conditions after corona restriction, all samples were negative in terms of the presence of SARS-CoV-2 on the surfaces of the nozzles. In spite of the fact that gas stations can be one of the foremost inclined places for the transmission and spread of coronavirus due to the nearness and visit of individuals, but through the observance of health behaviors and implementing some procedures, cutting the transmission chain in gas stations can be facilitated.

Investigation of SARS-CoV-2 in hospital indoor air of COVID-19 patients' ward with impinger method.

In December 2019, all nations learnt about the emergence of a pandemic of coronavirus disease (COVID-19), induced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is a member of the ß-coronavirus group. As SARS-CoV-2 has the potentiality of leading to life-threatening respiratory failure, its transmission routes need to be characterized. Yet, the possibility of airborne transmission is still debated. This study was performed to evaluate potential hospital indoor air viral quality in order to detect SARS-COV-2. For this purpose, an impinger method was used to monitor the SARS-COV-2 virus in the air. Thus, 33 samples were collected from 8 different hospital locations. The sampling time was between 50 and 60 min with a sampling flow rate of 28 L/min. Air samples were taken from 2 to 5 m away from the patients' beds. Temperature, relative humidity, and CO2 concentration were 28, 37, and 438 ppm, respectively. The results indicated that air samples which were 2 to 5 m away from the patients' beds were negative for the presence of the virus. According to the obtained results, it is suggested that airborne transmission may not have much effect on this pandemic. However, as the patients with SARS-CoV-2 were hospitalized in rooms with negative air pressure, the results might have been negatively affected. Graphical abstract.

Immune and bioinformatics identification of T cell and B cell epitopes in the protein structure of SARS-CoV-2: A systematic review.

The beginning of 2020 was marked as the emergence of a COVID-19 outbreak caused by a new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, there is no vaccine or approved treatment for this infectious virus so the invention of an efficient vaccine is certainly a high priority. Some studies have employed several techniques to facilitate the combination of the immunoinformatics approach and comparative genomic approach in order to determine the potential peptides for designing the T-cell epitope-based peptide vaccine using the 2019-nCoV envelope protein as a target. Via screening the bioimmunoinformatic SARS-CoV2 derived B-cell and T-cell epitopes within the basic immunogenic of SARS-CoV2 proteins, we presented a set of inferred B-cell and T-cell epitopes from the spike (S) and nucleocapsid (N) proteins with high antigenicity and without allergenic property or toxic effects. Our findings provide a screened set of epitopes that can be introduced as potential targets for developing peptide vaccines against the SARS-CoV-2 virus.

What family doctors know about congenital CMV: a regional survey in Iran.

BACKGROUND: Since there is no effective treatment or vaccine against the congenital cytomegalovirus (cCMV) infection, knowledge and awareness of medical doctor's (MDs) especially family doctors are essential for preventive strategies and it also seems to be usually ignored by healthcare providers. Aim of this study was to investigate awareness of MDs about cCMV infection in Iran. METHODS: A single page questionnaire was randomly distributed among 450 MDs including general practitioners, pediatricians, gynecologists, internal and other medical specialists concerning of their knowledge in clinical presentation, diagnosis, prevention, prognosis, epidemiology, transmission, and management of cCMV infection. All statistical analyses were performed using SPSS version 16. RESULTS: More than half of questionnaire recipients refused to take part in any of the questionnaire items. The most of the respondents were agreed for newborn CMV screening tests and mandatory CMV test for women trying to get pregnant, which, are not routinely tested. The knowledge of general practitioners about cCMV was less than usual. The field of expertise had a profound effect in this survey, but age and gender did not. CONCLUSIONS: Our results indicated that the knowledge of cCMV infection, especially among family doctors contains several gaps. Urgent action is required to improve family doctor's knowledge of CMV infection. Surveys to evaluate CMV awareness among MDs, healthcare professionals and women of childbearing age are proposed.

Echovirus 30 and coxsackievirus A9 infection among young neonates with sepsis in Iran.

BACKGROUND AND OBJECTIVES: Human enteroviruses (EV) are the most common causes of neonatal sepsis-like disease. The frequencies of EV including coxsackievirus A, coxsackievirus B and Echovirus serotypes have been studied in young infants (younger than three months) with sepsis. So far, the role of enteroviruses among neonates with sepsis was not determined in Ahvaz, Iran. Therefore, this study was aimed to evaluate the frequency of EV among hospitalized young infants with clinical signs and symptoms of sepsis in Ahvaz. MATERIALS AND METHODS: Blood specimens from 128 neonates (younger than 90 days), including 56 (43.75%) girls and 72 (56.25%) boys, were collected from hospitalized neonates with clinical signs and symptoms of sepsis-like symptoms. All blood samples were negative for bacterial culture. RNA was extracted from all sera and tested for detection of 5'UTR (Untranslated Region) of the EV by RT-PCR. To determine specific strains of EV, positive 5'UTR samples were further tested for detection of the VP1 region of EV by RT-PCR. RESULTS: Overall, 50/128 (39.06%) specimens, including 24 (48%) girls and 26 (52%) boys, were positive for EV. 21/50 (42%) specimens were positive for the VP1 region. Randomly, 8 positive VP1 were selected and sequenced. Analysis of sequencing data showed 7/21 (33.33%) samples were positive for Echovirus 30 and 1/21 (4.76%) samples were positive for CVA9. CONCLUSION: The results of this survey indicate high prevalence of 39.06% of EV among young neonates with sepsis. A high prevalence of 33.3% Echoviruses 30 and a low rate of 4.76% coxsackievirus A9 infection has been observed in neonatal patients with viral sepsis. This outbreak is probably one of the first Enterovirus outbreaks to be reported in Ahvaz, Iran. The results of this survey will help to minimize unneeded use of antimicrobial drugs and reduce unnecessary hospitalization.