Plasma Virome of HIV-infected Subjects on Suppressive Antiretroviral Therapy Reveals Association of Differentially Abundant Viruses with Distinct T-cell Phenotypes and Inflammation.

Background: The plasma virome represents the overall composition of viral sequences present in it. Alteration in plasma virome has been reported in treatment naïve and immunocompromised (CD4 count < 200) people with HIV (PWH). However, the effect of ART on virome composition in PWH on ART with preserved CD4 counts is poorly understood. Objectives: We aimed to assess the alterations in plasma virome in PWH on ART in comparison to HIV-negative uninfected controls and to further investigate possible associations of plasma viruses with inflammation and immune dysfunction, namely, immunosenescence and immune exhaustion. Methods: Plasma viral DNA from PWH on ART and controls was used for sequencing on the Illumina Nextseq500 platform, followed by the identification of viral sequences using an automated pipeline, VIROMATCH. Multiplex cytokine assay was performed to measure the concentrations of various cytokines in plasma. Immunophenotyping was performed on PBMCs to identify T cell markers of immunosenescence and immune exhaustion. Results: In our observational, cross-sectional pilot study, chronically infected PWH on ART had significantly different viral species compositions compared to controls. The plasma virome of PWH showed a significantly high relative abundance of species Human gammaherpesvirus 4, also known as Epstein-Barr virus (EBV). Moreover, EBV emerged as a significant viral taxon differentially enriched in PWH on ART, which further correlated positively with the exhaustion phenotype of T cells and significantly increased TNF-α in PWH on ART. Additionally, a significantly increased proportion of senescent T cells and IL-8 cytokine was detected in PWH on ART. Conclusion: Altered plasma virome influenced the inflammatory response and T-cell phenotype in PWH on ART.

Exploring the Human Virome: Composition, Dynamics, and Implications for Health and Disease.

Humans are colonized by large number of microorganisms-bacteria, fungi, and viruses. The overall genome of entire viruses that either lives on or inside the human body makes up the human virome and is indeed an essential fraction of the human metagenome. Humans are constantly exposed to viruses as they are ubiquitously present on earth. The human virobiota encompasses eukaryotic viruses, bacteriophages, retroviruses, and even giant viruses. With the advent of Next-generation sequencing (NGS) and ongoing development of numerous bioinformatic softwares, identification and taxonomic characterization of viruses have become easier. The viruses are abundantly present in humans; these can be pathogenic or commensal. The viral communities occupy various niches in the human body. The viruses start colonizing the infant gut soon after birth in a stepwise fashion and the viral composition diversify according to their feeding habits. Various factors such as diet, age, medications, etc. influence and shape the human virome. The viruses interact with the host immune system and these interactions have beneficial or detrimental effects on their host. The virome composition and abundance change during the course of disease and these alterations impact the immune system. Hence, the virome population in healthy and disease conditions influences the human host in numerous ways. This review presents an overview of assembly and composition of the human virome in healthy asymptomatic individuals, changes in the virome profiles, and host-virome interactions in various disease states.

Transcriptional landscape of long non-coding RNAs (lncRNAs) and its implication in viral diseases.

Long non-coding RNAs (lncRNAs) are RNA transcripts of size >200 bp that do not translate into proteins. Emerging data revealed that viral infection results in systemic changes in the host at transcriptional level. These include alterations in the lncRNA expression levels and triggering of antiviral immune response involving several effector molecules and diverse signalling pathways. Thus, lncRNAs have emerged as an essential mediatory element at distinct phases of the virus infection cycle. The complete eradication of the viral disease requires more precise and novel approach, thus manipulation of the lncRNAs could be one of them. This review shed light upon the existing knowledge of lncRNAs wherein the implication of differentially expressed lncRNAs in blood-borne, air-borne, and vector-borne viral diseases and its promising therapeutic applications under clinical settings has been discussed. It further enhances our understanding of the complex interplay at host-pathogen interface with respect to lncRNA expression and function.

Short-Chain Fatty Acid (SCFA) as a Connecting Link between Microbiota and Gut-Lung Axis-A Potential Therapeutic Intervention to Improve Lung Health.

The microbiome is an integral part of the human gut, and it plays a crucial role in the development of the immune system and homeostasis. Apart from the gut microbiome, the airway microbial community also forms a distinct and crucial part of the human microbiota. Furthermore, several studies indicate the existence of communication between the gut microbiome and their metabolites with the lung airways, called "gut-lung axis". Perturbations in gut microbiota composition, termed dysbiosis, can have acute and chronic effects on the pathophysiology of lung diseases. Microbes and their metabolites in lung stimulate various innate immune pathways, which modulate the expression of the inflammatory genes in pulmonary leukocytes. For instance, gut microbiota-derived metabolites such as short-chain fatty acids can suppress lung inflammation through the activation of G protein-coupled receptors (free fatty acid receptors) and can also inhibit histone deacetylase, which in turn influences the severity of acute and chronic respiratory diseases. Thus, modulation of the gut microbiome composition through probiotic/prebiotic usage and fecal microbiota transplantation can lead to alterations in lung homeostasis and immunity. The resulting manipulation of immune cells function through microbiota and their key metabolites paves the way for the development of novel therapeutic strategies in improving the lung health of individuals affected with various lung diseases including SARS-CoV-2. This review will shed light upon the mechanistic aspect of immune system programming through gut and lung microbiota and exploration of the relationship between gut-lung microbiome and also highlight the therapeutic potential of gut microbiota-derived metabolites in the management of respiratory diseases.