Tetraspanins are transmembrane glycoproteins that have been shown increasing interest as host factors in infectious diseases. In particular, they were implicated in the pathogenesis of both non-enveloped (human papillomavirus (HPV)) and enveloped (human immunodeficiency virus (HIV), Zika, influenza A virus, (IAV), and coronavirus) viruses through multiple stages of infection, from the initial cell membrane attachment to the syncytium formation and viral particle release. However, the mechanisms by which different tetraspanins mediate their effects vary. This review aimed to compare and contrast the role of tetraspanins in the life cycles of HPV, HIV, Zika, IAV, and coronavirus viruses, which cause the most significant health and economic burdens to society. In doing so, a better understanding of the relative contribution of tetraspanins in virus infection will allow for a more targeted approach in the treatment of these diseases.

Integrins are a large family of transmembrane heterodimeric proteins that constitute the main receptors for extracellular matrix components. Integrins were initially thought to be primarily involved in the maintenance of cell adhesion and tissue integrity. However, it is now appreciated that integrins play important roles in many other biological processes such as cell survival, proliferation, differentiation, migration, cell shape and polarity. Lung cells express numerous combinations and permutations of integrin heterodimers. The complexity and diversity of different integrin heterodimers being implicated in different lung diseases present a major challenge for drug development. Here we provide a comprehensive overview of the current knowledge of integrins from studies in cell culture to integrin knockout mouse models and provide an update of results from clinical trials for which integrins are therapeutic targets with a focus on respiratory diseases (asthma, emphysema, pneumonia, lung cancer, pulmonary fibrosis and sarcoidosis).

Increased airway smooth muscle (ASM) mass is believed to underlie the relatively fixed airway hyperresponsiveness (AHR) in asthma. Developments of therapeutic approaches to reverse airway remodeling are impeded by our lack of insight on the mechanisms behind the increase in mass of contractile ASM cells. Increased expression of laminin, an extracellular matrix protein, is associated with asthma. Our studies investigate the role of laminin‐induced ASM survival signals in the development of increased ASM and AHR. Antagonizing laminin integrin binding using the laminin‐selective competing peptide, YIGSR, and mimicking laminin with exogenous α2‐chain laminin, we show that laminin is both necessary and sufficient to induce ASM cell survival, concomitant with the induction of ASM contractile phenotype. Using siRNA, we show that the laminin‐binding integrin α7β1 mediates this process. Moreover, in laminin‐211‐deficient mice, allergen‐induced AHR was not observed. Notably, ASM cells from asthmatic airways express a higher abundance of intracellular cell survival proteins, consistent with a role for reduced rates of cell apoptosis in development of ASM hyperplasia. Targeting the laminin‐integrin α7β1 signaling pathway may offer new avenues for the development of therapies to reduce the increase in mass of contractile phenotype ASM cells that underlie AHR in asthma.—Tran, T., Teoh, C. M., Tam, J. K. C., Qiao, Y., Chin, C. Y., Chong, O. K., Stewart, A. G., Harris, T., Wong, W. S. F., Guan, S. P., Leung, B. P., Gerthoffer, W. T., Unruh, H., and Halayko, A J. Laminin drives survival signals to promote a contractile smooth muscle phenotype and airway hyperreactivity. FASEB J. 27, 3991–4003 (2013). www.fasebj.org