Acute respiratory viral infections in COVID-19 pandemic in practice of polyclinic doctor

Acute respiratory viral infections (ARVI), including influenza, remain the most common infectious diseases. In the context of COVID‑19 pandemic, there is a need for differential diagnosis of respiratory syndrome. The clinic of ARVI, depending on the pathogen, may have its own characteristics. Influenza and COVID‑19 have common pathways of transmission of the pathogen and similar symptoms, so the optimal differential diagnosis is the use of test systems for both viruses. Against the background of influenza and other acute respiratory infections, complications from various organs and systems can develop. The article discusses in detail the issues of the clinical course of ARVI, differential diagnosis, modern approaches to therapyand prophylactic. Complications of influenza from the cardiovascular system are considered in detail. The data of our own observations on the risk of developing acute coronary syndrome in persons who have undergone COVID‑19 are presented. Prevention of the development of complications of influenza and other acute respiratory infections is the early appointment of antiviral therapy. Numerous studies confirm the effectiveness of interferon inducers in the treatment of influenza and other ARVI. The article presents the results of clinical studies confirming the effectiveness of therapy with the interferon inducer Kagocel. Against the background of its use, a decrease in the severity of clinical manifestations, a reduction in the duration of the disease, and the prevention of complications were noted. In studies, the drug has shown a high level of safety. The article discusses studies on the effectiveness of chemoprophylaxis of influenza and other acute respiratory infections.

SARS-CoV-2 Spike Protein Suppresses ACE2 and Type I Interferon Expression in Primary Cells From Macaque Lung Bronchoalveolar Lavage

SARS-CoV-2 virus causes upper and lower respiratory diseases including pneumonia, and in some cases, leads to lethal pulmonary failure. Angiotensin converting enzyme-2 (ACE2), the receptor for cellular entry of SARS-CoV-2 virus, has been shown to protect against severe acute lung failure. Here, we provide evidence that SARS-CoV-2 spike protein S1 reduced the mRNA expression of ACE2 and type I interferons in primary cells of lung bronchoalveolar lavage (BAL) from naïve rhesus macaques. The expression levels of ACE2 and type I interferons were also found to be correlated with each other, consistent with the recent finding that ACE2 is an interferon-inducible gene. Furthermore, induction of ACE2 and type I interferons by poly I:C, an interferon inducer, was suppressed by S1 protein in primary cells of BAL. These observations suggest that the downregulation of ACE2 and type I interferons induced by S1 protein may directly contribute to SARS-CoV-2-associated lung diseases.

Interferon Inducer IFI35 regulates RIG-I-mediated innate antiviral response through mutual antagonism with Influenza protein NS1

Interferon-stimulated genes (ISGs) create multiple lines of defense against viral infection. Here we show that interferon induced protein 35 (IFI35) inhibits swine (H3N2) influenza virus replication by directly interacting with the viral protein NS1. IFI35 binds more preferentially to the effector domain of NS1 (128-207aa) than to the viral RNA sensor RIG-I. This promotes mutual antagonism between IFI35 and NS1, and frees RIG-I from IFI35-mediated K48-linked ubiquitination and degradation. However, IFI35 does not interact with the NS1 encoded by avian (H7N9) influenza virus, resulting in IFI35 playing an opposite virus enabling role during highly pathogenic H7N9 virus infection. Notably, replacing the 128-207aa region of NS1-H7N9 with the corresponding region of NS1-H3N2 results in the chimeric NS1 acquiring the ability to bind to and mutually antagonize IFI35. IFI35 deficient mice accordingly exhibit more resistance to lethal H7N9 infection than their wild-type control exhibit. Our data uncover a novel mechanism by which IFI35 regulates RIG-I-mediated anti-viral immunity through mutual antagonism with influenza protein NS1. IMPORTANCE IAV infection poses a global health threat, and is among the most common contagious pathogens to cause severe respiratory infections in humans and animals. ISGs play a key role in host defense against IAV infection. In line with others, we show IFI35-mediated ubiquitination of RIG-I to be involved in innate immunity. Moreover, we define a novel role of IFI35 in regulating the type I IFN pathway during IAV infection. We found that IFI35 regulates RIG-I mediated antiviral signaling by interacting with IAV-NS1. H3N2 NS1, but notably not H7N9 NS1, interacts with IFI35 and efficiently suppresses IFI35-dependent ubiquitination of RIG-I. IFI35 deficiency protected mice from H7N9 virus infection. Therefore, manipulation of the IFI35-NS1 provides a new approach for the development of anti-IAV treatments.

Caprine MAVS Is a RIG-I Interacting Type I Interferon Inducer Downregulated by Peste des Petits Ruminants Virus Infection

The mitochondrial antiviral-signaling protein (MAVS, also known as VISA, IPS-1, or CARDIF) plays an essential role in the type I interferon (IFN) response and in retinoic acid-inducible gene I (RIG-I) mediated antiviral innate immunity in mammals. In this study, the caprine MAVS gene (caMAVS, 1566 bp) was identified and cloned. The caMAVS shares the highest amino acid similarity (98.1%) with the predicted sheep MAVS. Confocal microscopy analysis of partial deletion mutants of caMAVS revealed that the transmembrane and the so-called Non-Characterized domains are indispensable for intracellular localization to mitochondria. Overexpression of caMAVS in caprine endometrial epithelial cells up-regulated the mRNA levels of caprine interferon-stimulated genes. We concluded that caprine MAVS mediates the activation of the type I IFN pathway. We further demonstrated that both the CARD-like domain and the transmembrane domain of caMAVS were essential for the activation of the IFN-β promotor. The interaction between caMAVS and caprine RIG-I and the vital role of the CARD and NC domain in this interaction was demonstrated by co-immunoprecipitation. Upon infection with the Peste des Petits Ruminants Virus (PPRV, genus Morbillivirus), the level of MAVS was greatly reduced. This reduction was prevented by the addition of the proteasome inhibitor MG132. Moreover, we found that viral protein V could interact and colocalize with MAVS. Together, we identified caMAVS as a RIG-I interactive protein involved in the activation of type I IFN pathways in caprine cells and as a target for PPRV immune evasion.

Estimation of the efficiency of using interferon inducer in children with Epstein-Barr viral infection

The aim of the research. To evaluate the effectiveness of synthetic low-molecular interferon inducers in children with Epstein-Barr viral infection. Material and methods. The study included 68 children aged 7 to 17 years with primary Epstein-Barr viral infection: 38 children in the main group received basic therapy against the primary form of Epstein-Barr viral infection in age-specific dosages in combination with a synthetic low-molecular interferon inducer; 30 children of the control group received the conventional basic therapy with age-specific dosages. Results. It has been established that clinical manifestation of Epstein-Barr viral infection is based on immunopathological inflammation mediated by the factors of cellular immunity. As a result of the therapy, 78.95 % of children in the main group had a normal rate of functional recovery of the liver. In the control group, however, the recovery was delayed in 60.00 % of children: rapid recovery was only noted in the main group. Administration of synthetic lowmolecular weight interferon inducers in addition to basic symptomatic therapy facilitated the reduction of intoxication symptoms duration by 4.7±1.9 days (p < 0.05) and the duration of the icteric period by 5.3±0.9 days (p < 0.05), as well as 5.1±1.3 days earlier normalisation of liver size (p < 0.05). Conclusion. Thus, the use of synthetic low molecular weight interferon inducers in combination with basic therapy against the primary form of Epstein-Barr viral infection in children contributes to a faster restoration of the functional state of the liver. The conducted clinical and biochemical studies indicate high efficiency of synthetic low molecular weight interferon inducers in the complex therapy of Epstein-Barr viral infection in children.

Antiviral Activity of Kagocel® on the Model of Experimental Lethal Influenza Infection

Despite the obvious advances in vaccination and therapy, influenza remains a poorly controlled infection with high morbidity and mortality. This study examined the antiviral activity of interferon inducer Kagocel on a mouse model of lethal influenza pneumonia. It has been shown that the therapeutic and prophylactic use of Kagocel leads to a dose-dependent decrease in specific mortality and suppression of virus reproduction in lung tissue. The effect of Kagocel was statistically identical to the effect of the reference drug — Arbidol (umifenovir).

Outlooks of therapy for genital herpes

Herpesvirus infections are widespread in humans. Approximately 6–10% of adults suffer from genital herpes and 10–20% of them have recurrent disease. Herpesvirus infections (including asymptomatic and silent forms) were found to have a negative effect on human reproductive health. Herpes simplex virus can infect germ cells, impair spermatogenesis, and play a certain pathogenetic role in the development of infertility. Herpes is a serious medical and social problem. Patients with recurrent herpes often have imbalanced immune responses involving interferons and other cytokines, as well as inhibition of cellular and phagocytic reactions of the organism. Meglumine acridone acetate, an interferon inducer, demonstrated high clinical and immunological efficacy in the treatment and prevention of recurrent herpes. The drug can be combined with other medications and is well tolerated by patients. Key words: immune response, immunomodulators, recurrent herpesvirus infections, efficacy of meglumine acridone acetate