Cellular Sensors and Viral Countermeasures: A Molecular Arms Race between Host and SARS-CoV-2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19) pandemic that has caused disastrous effects on the society and human health globally. SARS-CoV-2 is a sarbecovirus in the Coronaviridae family with a positive-sense single-stranded RNA genome. It mainly replicates in the cytoplasm and viral components including RNAs and proteins can be sensed by pattern recognition receptors including toll-like receptors (TLRs), RIG-I-like receptors (RLRs), and NOD-like receptors (NLRs) that regulate the host innate and adaptive immune responses. On the other hand, the SARS-CoV-2 genome encodes multiple proteins that can antagonize the host immune response to facilitate viral replication. In this review, we discuss the current knowledge on host sensors and viral countermeasures against host innate immune response to provide insights on virus–host interactions and novel approaches to modulate host inflammation and antiviral responses

The emerging novel Middle East respiratory syndrome coronavirus: The “knowns” and “unknowns”

A novel lineage C betacoronavirus, originally named human coronavirus EMC/2012 (HCoV-EMC) and recently renamed Middle East respiratory syndrome coronavirus (MERS-CoV), that is phylogenetically closely related to Tylonycteris bat coronavirus HKU4 and Pipistrellus bat coronavirus HKU5, which we discovered in 2007 from bats in Hong Kong, has recently emerged in the Middle East to cause a severe acute respiratory syndrome (SARS)-like infection in humans. The first laboratory-confirmed case, which involved a 60-year-old man from Bisha, the Kingdom of Saudi Arabia (KSA), who died of rapidly progressive community-acquired pneumonia and acute renal failure, was announced by the World Health Organization (WHO) on September 23, 2012. Since then, a total of 70 cases, including 39 fatalities, have been reported in the Middle East and Europe. Recent clusters involving epidemiologically-linked household contacts and hospital contacts in the Middle East, Europe, and Africa strongly suggested possible human-to-human transmission. Clinical and laboratory research data generated in the past few months have provided new insights into the possible animal reservoirs, transmissibility, and virulence of MERS-CoV, and the optimal laboratory diagnostic options and potential antiviral targets for MERS-CoV-associated infection

Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan

A mysterious outbreak of atypical pneumonia in late 2019 was traced to a seafood wholesale market in Wuhan of China. Within a few weeks, a novel coronavirus tentatively named as 2019 novel coronavirus (2019-nCoV) was announced by the World Health Organization. We performed bioinformatics analysis on a virus genome from a patient with 2019-nCoV infection and compared it with other related coronavirus genomes. Overall, the genome of 2019-nCoV has 89% nucleotide identity with bat SARS-like-CoVZXC21 and 82% with that of human SARS-CoV. The phylogenetic trees of their orf1a/b, Spike, Envelope, Membrane and Nucleoprotein also clustered closely with those of the bat, civet and human SARS coronaviruses. However, the external subdomain of Spike’s receptor binding domain of 2019-nCoV shares only 40% amino acid identity with other SARS-related coronaviruses. Remarkably, its orf3b encodes a completely novel short protein. Furthermore, its new orf8 likely encodes a secreted protein with an alpha-helix, following with a beta-sheet(s) containing six strands. Learning from the roles of civet in SARS and camel in MERS, hunting for the animal source of 2019-nCoV and its more ancestral virus would be important for understanding the origin and evolution of this novel lineage B betacoronavirus. These findings provide the basis for starting further studies on the pathogenesis, and optimizing the design of diagnostic, antiviral and vaccination strategies for this emerging infection

Molecular prevalence and subtyping of Cryptosporidium hominis among captive long-tailed macaques (Macaca fascicularis) and rhesus macaques (Macaca mulatta) from Hainan Island, southern China

Abstract Background Cryptosporidium is an important zoonotic parasite that is commonly found in non-human primates (NHPs). Consequently, there is the potential for transmission of this pathogen from NHPs to humans. However, molecular characterization of the isolates of Cryptosporidium from NHPs remains relatively poor. The aim of the present work was to (i) determine the prevalence; and (ii) perform a genetic characterization of the Cryptosporidium isolated from captive Macaca fascicularis and M. mulatta on Hainan Island in southern China. Methods A total of 223 fresh fecal samples were collected from captive M. fascicularis (n = 193) and M. mulatta (n = 30). The fecal specimens were examined for the presence of Cryptosporidium spp. by polymerase chain reaction (PCR) and sequencing of the partial small subunit (SSU) rRNA gene. The Cryptosporidium-positive specimens were subtyped by analyzing the 60-kDa glycoprotein (gp60) gene sequence. Results Cryptosporidium spp. were detected in 5.7% (11/193) of M. fascicularis. All of the 11 Cryptosporidium isolates were identified as C. hominis. Subtyping of nine of these isolates identified four unique gp60 subtypes of C. hominis. These included IaA20R3a (n = 1), IoA17a (n = 1), IoA17b (n = 1), and IiA17 (n = 6). Notably, subtypes IaA20R3a, IoA17a, and IoA17b were novel subtypes which have not been reported previously. Conclusions To our knowledge, this is the first reported detection of Cryptosporidium in captive M. fascicularis from Hainan Island. The molecular characteristics and subtypes of the isolates here provide novel insights into the genotypic variation in C. hominis

Fatal pancytopenia due to albendazole treatment for strongyloidiasis

We report 7 cases of strongyloidiasis that had occurred from 2016 through 2017 in a tertiary hospital of southern China. Three of the 7 patients (age 66–77) with farming exposure many years ago developed symptomatic infection while receiving immunosuppressant for underlying medical conditions. The majority of them were treated with albendazole due to unavailability of ivermectin in mainland China. One of the 7 patients, with underlying IgG4 sclerosing cholangitis and secondary biliary cirrhosis was on immunosuppressives and developed severe pancytopenia 15 days after albendazole treatment. He ultimately died of polymicrobial sepsis. This was the second fatal case being reported in the literature as a consequence of albendazole-induced myelosuppression. We have undertaken a review of the literature regarding the use of albendazole for strongyloidiasis and its adverse effect with a focus on myelosuppression as a rare but potentially serious event. Keywords: Strongyloidiasis, Immunocompromised, Albendazole, Adverse effect, Pancytopeni