Insight into the emerging role of SARS-CoV-2 nonstructural and accessory proteins in modulation of multiple mechanisms of host innate defense.

Coronavirus disease-19 (COVID-19) is an extremely infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has become a major global health concern. The induction of a coordinated immune response is crucial to the elimination of any pathogenic infection. However, SARS-CoV-2 can modulate the host immune system to favor viral adaptation and persistence within the host. The virus can counteract type I interferon (IFN-I) production, attenuating IFN-I signaling pathway activation and disrupting antigen presentation. Simultaneously, SARS-CoV-2 infection can enhance apoptosis and the production of inflammatory mediators, which ultimately results in increased disease severity. SARS-CoV-2 produces an array of effector molecules, including nonstructural proteins (NSPs) and open-reading frames (ORFs) accessory proteins. We describe the complex molecular interplay of SARS-CoV-2 NSPs and accessory proteins with the host's signaling mediating immune evasion in the current review. In addition, the crucial role played by immunomodulation therapy to address immune evasion is discussed. Thus, the current review can provide new directions for the development of vaccines and specific therapies.

Intelligent Mechanisms of Macrophage Apoptosis Subversion by Mycobacterium.

Macrophages are one of the first innate defense barriers and play an indispensable role in communication between innate and adaptive immune responses, leading to restricted Mycobacterium tuberculosis (Mtb) infection. The macrophages can undergo programmed cell death (apoptosis), which is a crucial step to limit the intracellular growth of bacilli by liberating them into extracellular milieu in the form of apoptotic bodies. These bodies can be taken up by the macrophages for the further degradation of bacilli or by the dendritic cells, thereby leading to the activation of T lymphocytes. However, Mtb has the ability to interplay with complex signaling networks to subvert macrophage apoptosis. Here, we describe the intelligent strategies of Mtb inhibition of macrophages apoptosis. This review provides a platform for the future study of unrevealed Mtb anti-apoptotic mechanisms and the design of therapeutic interventions.

Human cytomegalovirus-encoded MicroRNAs: A master regulator of latent infection.

Human cytomegalovirus (HCMV) can modulate the host cell microenvironment to cause latent infection and is therefore considered a major health concern in immunocompromised patients. HCMV-encoded microRNAs (miRs) have emerged as a key player in regulating the expression of the host cell and viral genes to induce latent infection. HCMV-encoded miRs can inhibit antiviral immune responses, such as proinflammatory mediators production, antigenic presentation, and apoptosis. In addition, HCMV miRs can reduce viral DNA replication. In this review, we describe the mechanisms underlying HCMV-encoded miR-mediated regulation of latent infection that may be exploited for future designing novel miRs-directed therapies.