Middle East Respiratory Syndrome Coronavirus Outbreaks

Middle East respiratory syndrome coronavirus (MERS-CoV) is a single-stranded RNA-enveloped virus that belongs to the Coronaviridae family. Initially reported in 2012 in Saudi Arabia, MERS-CoV is a zoonotic virus originating from bats and transmitted from camels to humans and among humans by contact. It causes both upper and lower respiratory tract infections and in some instances can lead to renal failure or death. This chapter provides an overview of the virologic aspects, outbreaks and risk factors, clinical symptoms, diagnostic methods, as well as prevention and management of MERS-CoV infection

HIV/SIV Infection Primes Monocytes and Dendritic Cells for Apoptosis

Subversion or exacerbation of antigen-presenting cells (APC) death modulates host/pathogen equilibrium. We demonstrated during in vitro differentiation of monocyte-derived macrophages and monocyte-derived dendritic cells (DCs) that HIV sensitizes the cells to undergo apoptosis in response to TRAIL and FasL, respectively. In addition, we found that HIV-1 increased the levels of pro-apoptotic Bax and Bak molecules and decreased the levels of anti-apoptotic Mcl-1 and FLIP proteins. To assess the relevance of these observations in the context of an experimental model of HIV infection, we investigated the death of APC during pathogenic SIV-infection in rhesus macaques (RMs). We demonstrated increased apoptosis, during the acute phase, of both peripheral blood DCs and monocytes (CD14+) from SIV+RMs, associated with a dysregulation in the balance of pro- and anti-apoptotic molecules. Caspase-inhibitor and death receptors antagonists prevented apoptosis of APCs from SIV+RMs. Furthermore, increased levels of FasL in the sera of pathogenic SIV+RMs were detected, compared to non-pathogenic SIV infection of African green monkey. We suggest that inappropriate apoptosis of antigen-presenting cells may contribute to dysregulation of cellular immunity early in the process of HIV/SIV infection

Nosocomial outbreak of the Middle East Respiratory Syndrome coronavirus: a phylogenetic, epidemiological, clinical and infection control analysis

Background: Middle East Respiratory Syndrome coronavirus (MERS-CoV) continues to cause intermittent community and nosocomial outbreaks. Obtaining data on specific source(s) and transmission dynamics of MERS-CoV during nosocomial outbreaks has been challenging. We performed a clinical, epidemiological and phylogenetic investigation of an outbreak of MERS-CoV at a University Hospital in Riyadh, Kingdom of Saudi Arabia. Methods: Clinical, epidemiological and infection control data were obtained from patients and Healthcare workers (HCWs). Full genome sequencing was conducted on nucleic acid extracted directly from MERS-CoV PCR-confirmed clinical samples and phylogenetic analysis performed. Phylogenetic analysis combined with published MERS-CoV genomes was performed. HCWs compliance with infection control practices was also assessed. Results: Of 235 persons investigated, there were 23 laboratory confirmed MERS cases, 10 were inpatients and 13 HCWs. Eight of 10 MERS inpatients died (80% mortality). There were no deaths among HCWs. The primary index case assumed from epidemiological investigation was not substantiated phylogenetically. 17/18 of MERS cases were linked both phylogenetically and epidemiologically. One asymptomatic HCW yielded a MERS-CoV genome not directly linked to any other case in the investigation. Five HCWs with mild symptoms yielded >75% full MERS-CoV genome sequences. HCW compliance with use of gowns was 62.1%, gloves 69.7%, and masks 57.6%. Conclusions: Several factors and sources, including a HCW MERS-CoV ‘carrier phenomenon’, occur during nosocomial MERS-CoV outbreaks. Phylogenetic analyses of MERS-CoV linked to clinical and epidemiological information is essential for outbreak investigation. The specific role of apparently healthy HCWs in causing nosocomial outbreaks requires further definition

Desensitization to type I interferon in HIV-1 infection correlates with markers of immune activation and disease progression

Type I interferon (IFNα/β) plays a complex role in HIV-1 infection and has been proposed alternately to have roles in either disease protection or progression. Although IFNα/β plays crucial roles in regulating monocytes and dendritic cells, responsiveness of these cells to IFNα/β in HIV-1 infection is poorly understood. We report significant defects in IFNα/β receptor (IFNα/βR) expression, IFNα signaling, and IFNα-induced gene expression in monocytes from HIV-1–infected subjects. IFNα/βR expression correlated directly with CD4+ T-cell count and inversely with HIV-1 RNA level and expression of CD38 by memory (CD45RO+) CD8+ T cells, a measure of pathologic immune activation in HIV-1 infection associated with disease progression. In addition, monocytes from HIV-1–infected persons showed diminished responses to IFNα, including decreased induction of phosphorylated STAT1 and the classical interferon-stimulated gene produces MxA and OAS. These IFNα responses were decreased regardless of IFNα/βR expression, suggesting that regulation of intracellular signaling may contribute to unresponsiveness to IFNα/β in HIV-1 disease. Defective monocyte responses to IFNα/β may play an important role in the pathogenesis of HIV-1 infection, and decreased IFNα/βR expression may serve as a novel marker of disease progression