Aberrant T cell immunity triggered by human Respiratory Syncytial Virus and human Metapneumovirus infection

Abstract

Human Respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV) are the two major etiological viral agents of lower respiratory tract diseases, affecting mainly infants, young children and the elderly. Although the infection of both viruses trigger an antiviral immune response that mediate viral clearance and disease resolution in immunocompetent individuals, the promotion of long-term immunity appears to be deficient and reinfection are common throughout life. A possible explanation for this phenomenon is that hRSV and hMPV, can induce aberrant T cell responses, which leads to exacerbated lung inflammation and poor T and B cell memory immunity. The modulation of immune response exerted by both viruses include different strategies such as, impairment of immunological synapse mediated by viral proteins or soluble factors, and the induction of pro-inflammatory cytokines by epithelial cells, among others. All these viral strategies contribute to the alteration of the adaptive immunity in order to increase the susceptibility to reinfections.In this review, we discuss current research related to the mechanisms underlying the impairment of T and B cell immune responses induced by hRSV and hMPV infection. In addition, we described the role each virulence factor involved in immune modulation caused by these viruses.

Genetic characterization of human metapneumovirus identified through community and facility‐based surveillance of infants in Dhaka, Bangladesh

“…By contrast, there were only two hMPV‐positive cases between January and August 2016. While hMPV infection triggers an immediate antiviral immune response that does not promote long‐term immunity, the memory cells may protect infants from early second exposure. No seasonal pattern of hMPV infection was observed over the twenty‐one months’ study period.…”

Prophylactic and therapeutic approaches for human metapneumovirus

“…Knowledge of host immune response to HMPV infection is required to understand the immunopathology induced by the virus and further development of vaccines or therapeutics. Like any other virus, both innate and adaptive immune components are essential to clear the HMPV infection but it induces a weak memory response in the host [ 31 , 38 ]. Innate immune responses are the first line of defence against the viral infection and act by recognizing the pathogen associated molecular patterns (PAMPS) on the viral particles through the pattern recognition receptors (PRRs) present on the immune cells in the respiratory tracts.…”

Human Metapneumovirus Establishes Persistent Infection in Lung Microvascular Endothelial Cells and Primes a Th2-Skewed Immune Response

“…Persistence in the host and impairment of T cell activation are critical mechanisms that are exploited by HMPV to avoid virus clearance [ 14 ]. However, viral strategies that are used to circumvent the host immune system are still poorly understood.…”

“…Nasal washes from infants with upper or lower respiratory tract HMPV infection contain increased amount of interleukin (IL)-4 and lower levels of proinflammatory cytokines and IL-12 when compared to secretions that were obtained by children infected with other respiratory viruses [ 11 , 12 ]. Accordingly, the stimulation of peripheral blood mononuclear cells (PBMCs) obtained from experienced healthy subjects with HMPV induces a higher level of IL-6 (a cytokine that prevents Th1 differentiation) and a low level of interferon (IFN)-γ when compared to RSV [ 13 , 14 ]. In vivo, HMPV infection is associated with long-term pulmonary inflammation, which leads to significant obstructive disease of the airways [ 15 , 16 ].…”