Type I IFNs: A Blessing in Disguise or Partner in Crime in MERS-CoV-, SARS-CoV-, and SARS-CoV-2-Induced Pathology and Potential Use of Type I IFNs in Synergism with IFN-γ as a Novel Antiviral Approach Against COVID-19.

Since the end of 2019, the emergence of novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has accelerated the research on host immune responses toward the coronaviruses. When there is no approved drug or vaccine to use against these culprits, host immunity is the major strategy to fight such infections. Type I interferons are an integral part of the host innate immune system and define one of the first lines of innate immune defense against viral infections. The in vitro antiviral role of type I IFNs against Middle East respiratory syndrome coronavirus (MERS-CoV) and SARS-CoV (severe acute respiratory syndrome coronavirus) is well established. Moreover, the involvement of type I IFNs in disease pathology has also been reported. In this study, we have reviewed the protective and the immunopathogenic role of type I IFNs in the pathogenesis of MERS-CoV, SARS-CoV, and SARS-CoV-2. This review will also enlighten the potential implications of type I IFNs for the treatment of COVID-19 when used in combination with IFN-γ.

First Case Report on Quantification of Antimicrobial Use in Corporate Dairy Farms in Pakistan.

Intensive livestock farming has become indispensable to meet the rapidly increasing demand for animal-based nutrition in low- and middle-income countries (LMICs) where antimicrobials are frequently used for treatment and prophylactic or metaphylactic purposes. However, very little is known about the trends of antimicrobial use (AMU) in dairy animals in LMICs. The objective of this study was to quantify AMU in two large commercial dairy farms in Pakistan. A retrospective study was conducted at two large corporate commercial dairy farms located in Punjab province for the year 2018. AMU was calculated using three metrics: active ingredient (AI; kg) and milligrams per population unit (mg/PU; mg/kg), which quantifies the amount of AI used, and antimicrobial treatment incidence (ATI; DDDA/1,000 cow-days), which estimates the per-day number of treatments to 1,000 cows. Total on-farm AMU was found to be 138.34 kg, 65.88 mg/kg, and 47.71 DDDA/1,000 cow-days. Measured in ATI, aminoglycosides (11.05 DDDA/1,000 cow-days), penicillins (8.29 DDDA/1,000 cow-days), and tetracyclines (8.1 DDDA/1,000 cow-days) were the most frequently used antimicrobial classes. A total of 42.46% of all the antimicrobials used belonged to the critically important antimicrobials for human medicine as defined by the World Health Organization. Considerably high AMU was found compared to other farm-level studies across the world. This was the first study to quantify AMU in the dairy industry in Pakistan. Our results showed that corporate commercial dairy management practices are associated with increased antimicrobial consumption and highlight the need for antimicrobial stewardship programs to encourage prudent use of antimicrobials in commercial dairy.

Anti-chicken type I IFN countermeasures by major avian RNA viruses.

Chicken type I interferons (type I IFNs) are key antiviral players of the chicken innate immune system and are considered potent antiviral agents against avian viral pathogens. Chicken type I IFNs are divided into three subtypes namely, chIFN-α, chIFN-ß, and chIFN-κ. Viral pathogen-associated molecular patterns (PAMPs) recognized by their corresponding specific PRRs (pattern recognition receptors) induce the expression of chicken type I IFNs. Interaction of chicken type I IFNs with their subsequent IFN receptors results in the activation of the JAK-STAT pathway, which in turn activates hundreds of chicken interferon-stimulated genes (chISGs). These chISGs establish an antiviral state in neighboring cells and prevent the replication and dissemination of viruses within chicken cells. Chicken type I IFNs activate different pathways that constitute major antiviral innate defense mechanisms in chickens. However, evolutionary mechanisms in viruses have made them resistant to these antiviral players by manipulating host innate immune pathways. This review focuses on the underlying molecular mechanisms employed by avian RNA viruses to counteract chicken type I IFNs and chISGs through different viral proteins. This may help to understand host-pathogen interactions and the development of novel therapeutic strategies to control viral infections in poultry.

Antimicrobial profiling and molecular characterization of antibiotic resistant genes of Proteus vulgaris isolated from tertiary care hospital, Islamabad, Pakistan.

Urinary tract infections (UTIs) are among the most common bacterial infections acquired from hospitals and community. Pseudomonas and Proteus species are the common cause of these UTIs. Generally, UTIs are self-limiting but have potential to re-occur. Extensive treatment therapy with antibiotics lead to the development of resistance in uropathogens. The development of antibiotic resistance is leading to the failure of currently available antibiotic based therapies thus making the situation worse. The objective of the present study was to access antimicrobial sensitivity and to characterize antibiotic resistant genes of Proteus vulgaris (P. vulgaris) isolated from patients suffering with UTIs. A total of 150 urine samples were collected and cultured on MacConkey agar medium followed by isolation and identification on blood agar medium. Biochemical characterization of all presumptive Proteus isolates was done using Remel Rap ID one kit. Antibiotic sensitivity for P. vulgaris isolates was performed by disc diffusion method. Presence of blaTEM and qnr antibiotic resistant genes was determined by PCR. The results showed that the overall prevalence of P. vulgaris in clinical samples was 11.3%. It showed maximum resistance (94%) to three antibiotics i.e. ampicillin, tigecycline and chloramphenicol, while least resistance was observed against imipenem (12%). Statistical analysis depicted that imipenem had a significantly larger zone of inhibition (P=.01), while ampicillin had significantly smaller zone of inhibition (P=.0004) followed by chloramphenicol (p-value = 0.002). Imipenem should be considered as an effective antibiotic to treat urinary tract infections associated with P. vulgaris. Both blaTEM and qnr genes were found to be involved in conferring resistance to ß-lactam and quinolones antibiotics.