Sub-cellular Biochemistry

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The cholesterol of the host cell plasma membrane and viral M2 protein plays a crucial role in multiple stages of infection and replication of the influenza A virus. Cholesterol is required for the formation of heterogeneous membrane microdomains (or rafts) in the budozone of the host cell that serves as assembly sites for the viral components. The raft microstructures act as scaffolds for several proteins. Cholesterol may further contribute to the mechanical forces necessary for membrane scission in the last stage of budding and help to maintain the stability of the virus envelope...

Human endogenous retroviruses (HERVs), which are conserved sequences of ancient retroviruses, are widely distributed in the human genome. Although most HERVs have been rendered inactive by evolution, some have continued to exhibit important cytological functions. HERVs in the human genome perform dual functions: on the one hand, they are involved in important physiological processes such as placental development and immune regulation; on the other hand, their aberrant expression is closely associated with the pathological processes of several diseases, such as cancers, autoimmune diseases, and viral infections...

The frequent emergence of pathogenic viruses with pandemic potential has posed a significant threat to human health and economy, despite enormous advances in our understanding of infection mechanisms and devising countermeasures through developing various prophylactic and therapeutic strategies. The recent coronavirus disease (COVID-19) pandemic has re-emphasised the importance of rigorous research on virus infection mechanisms and highlighted the need for our preparedness for potential pandemics. Although viruses cannot self-replicate, they tap into host cell factors and processes for their entry, propagation and dissemination...

RNA is a central molecule in the life cycle of viruses, acting not only as messenger (m)RNA but also as a genome. Given these critical roles, it is not surprising that viral RNA is a hub for host-virus interactions. However, the interactome of viral RNAs remains largely unknown. This chapter discusses the importance of cellular RNA-binding proteins in virus infection and the emergent approaches developed to uncover and characterise them.

The cytoskeleton, which includes actin filaments, microtubules, and intermediate filaments, is one of the most important networks in the cell and undertakes many fundamental life activities. Among them, actin filaments are mainly responsible for maintaining cell shape and mediating cell movement, microtubules are in charge of coordinating all cargo transport within the cell, and intermediate filaments are mainly thought to guard against external mechanical pressure. In addition to this, cytoskeleton networks are also found to play an essential role in multiple viral infections...

African swine fever virus is a complex double-stranded DNA virus that exhibits tropism for cells of the mononuclear phagocytic system. Virus replication is a multi-step process that involves the nucleus of the host cell as well the formation of large perinuclear sites where progeny virions are assembled prior to transport to, and budding through, the plasma membrane. Like many viruses, African swine fever virus reorganises the cellular architecture to facilitate its replication and has evolved multiple mechanisms to avoid the potential deleterious effects of host cell stress response pathways...

RNA virus infections have been a leading cause of pandemics. Aided by global warming and increased connectivity, their threat is likely to increase over time. The flaviviruses are one such RNA virus family, and its prototypes such as the Japanese encephalitis virus (JEV), Dengue virus, Zika virus, West Nile virus, etc., pose a significant health burden on several endemic countries. All viruses start off their life cycle with an infected cell, wherein a series of events are set in motion as the virus and host battle for autonomy...

During respiratory syncytial virus (RSV) particle assembly, the mature RSV particles form as filamentous projections on the surface of RSV-infected cells. The RSV assembly process occurs at the / on the cell surface that is modified by a virus infection, involving a combination of several different host cell factors and cellular processes. This induces changes in the lipid composition and properties of these lipid microdomains, and the virus-induced activation of associated Rho GTPase signaling networks drives the remodeling of the underlying filamentous actin (F-actin) cytoskeleton network...

Human papillomavirus (HPV) is associated with infection of different tissues, such as the cervix, anus, vagina, penis, vulva, oropharynx, throat, tonsils, back of the tongue, skin, the lungs, among other tissues. HPV infection may or may not be associated with the development of cancer, where HPVs not related to cancer are defined as low-risk HPVs and are associated with papillomatosis disease. In contrast, high-risk HPVs (HR-HPVs) are associated with developing cancers in areas that HR-HPV infects, such as the cervix...

The cytopathic effect comprises the set of cellular alterations produced by a viral infection. It is of great relevance since it constitutes a direct marker of infection. Likewise, these alterations are often virus-specific which makes them a phenotypic marker for many viral species. All these characteristics have been used to complement the study of the dynamics of virus-cell interactions through the kinetic study of the progression of damage produced by the infection. Various approaches have been used to monitor the cytopathic effect, ranging from light microscopy, immunofluorescence assays, and direct labeling with fluorescent dyes, to plaque assay for the characterization of the infection over time...

Viruses are obligate intracellular pathogens that depend on their host cell machinery and metabolism for their replicative life cycle. Virus entry, replication, and assembly are dynamic processes that lead to the reorganisation of host cell components. Therefore, a complete understanding of the viral processes requires their study in the cellular context where advanced imaging has been proven valuable in providing the necessary information. Among the available imaging techniques, soft X-ray tomography (SXT) at cryogenic temperatures can provide three-dimensional mapping to 25 nm resolution and is ideally suited to visualise the internal organisation of virus-infected cells...

Novel imaging technologies such as single-particle tracking provide tools to study the intricate process of virus infection in host cells. In this chapter, we provide an overview of studies in which single-particle tracking technologies were applied for the analysis of the viral entry pathways in the context of the live host cell. Single-particle tracking techniques have been dependent on advances in the fluorescent labeling microscopy method and image analysis. The mechanistic and kinetic insights offered by this technique will provide a better understanding of virus entry and may lead to a rational design of antiviral interventions...

As obligate pathogens, viruses have developed diverse mechanisms to deliver their genome across host cell membranes to sites of virus replication. While enveloped viruses utilize viral fusion proteins to accomplish fusion of their envelope with the cellular membrane, non-enveloped viruses rely on machinery that causes local membrane ruptures and creates an opening through which the capsid or viral genome is released. Both membrane fusion and membrane penetration take place at the plasma membrane or in intracellular compartments, often involving the engagement of the cellular machinery and antagonism of host restriction factors...

Viruses are infectious entities that make use of the replication machinery of their hosts to produce more progenies, causing disease and sometimes death. To counter viral infection, metazoan hosts are equipped with various defense mechanisms, from the rapid-evoking innate immune responses to the most advanced adaptive immune responses. Previous research demonstrated that cells in fruit flies and mice infected with Drosophila C virus and influenza, respectively, undergo apoptosis, which triggers the engulfment of apoptotic virus-infected cells by phagocytes...

The immune system functions to protect the host from pathogens. To counter host defense mechanisms, pathogens have developed unique strategies to evade detection or restrict host immune responses. Programmed cell death is a major contributor to the multiple host responses that help to eliminate infected cells for obligate intracellular pathogens like viruses. Initiation of programmed cell death pathways during the early stages of viral infections is critical for organismal survival as it restricts the virus from replicating and serves to drive antiviral inflammation immune recruitment through the release of damage-associated molecular patterns (DAMPs) from the dying cell...

Cryo-electron tomography (cryo-ET) has emerged as a powerful tool in structural biology to study viruses and is undergoing a resolution revolution. Enveloped viruses comprise several RNA and DNA pleomorphic viruses that are pathogens of clinical importance to humans and animals. Considerable efforts in cryogenic correlative light and electron microscopy (cryo-CLEM), cryogenic focused ion beam milling (cryo-FIB), and integrative structural techniques are helping to identify virus structures within cells leading to a rise of in situ discoveries shedding light on how viruses interact with their hosts during different stages of infection...

Ageing is generally characterised by the declining ability to respond to stress, increasing homeostatic imbalance, and increased risk of ageing-associated diseases . Mechanistically, the lifelong accumulation of a wide range of molecular and cellular impairments leads to organismal senescence. The aging population poses a severe medical concern due to the burden it places on healthcare systems and the general public as well as the prevalence of diseases and impairments associated with old age. In this chapter, we discuss organ failure during ageing as well as ageing of the hypothalamic-pituitary-adrenal axis and drugs that can regulate it...

The gradual ageing of the world population has been accompanied by a dramatic increase in the prevalence of obesity and metabolic diseases, especially type 2 diabetes. The adipose tissue dysfunction associated with ageing and obesity shares many common physiological features, including increased oxidative stress and inflammation. Understanding the mechanisms responsible for adipose tissue dysfunction in obesity may help elucidate the processes that contribute to the metabolic disturbances that occur with ageing...

The proportion of elderly individuals is rising globally, and data have shown that as high as 8% of the elderly community suffer from malnutrition. Protein energy malnutrition has shown to elevate morbidity and mortality risk in the elderly; therefore, protein and energy supplement are needed for the elderly populations to create healthy conditions. This chapter describes about general structure of protein, protein turnover, amino acid metabolism including metabolism in the elderly, protein change in aging, supplementation of amino acid as well as vitamin and mineral for the elderly...