Journal of virology
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Journal of virology · Oct 2014
Rooting the phylogenetic tree of middle East respiratory syndrome coronavirus by characterization of a conspecific virus from an African bat.
The emerging Middle East respiratory syndrome coronavirus (MERS-CoV) causes lethal respiratory infections mainly on the Arabian Peninsula. The evolutionary origins of MERS-CoV are unknown. We determined the full genome sequence of a CoV directly from fecal material obtained from a South African Neoromicia capensis bat (NeoCoV). NeoCoV shared essential details of genome architecture with MERS-CoV. Eighty-five percent of the NeoCoV genome was identical to MERS-CoV at the nucleotide level. Based on taxonomic criteria, NeoCoV and MERS-CoV belonged to one viral species. The presence of a genetically divergent S1 subunit within the NeoCoV spike gene indicated that intraspike recombination events may have been involved in the emergence of MERS-CoV. NeoCoV constitutes a sister taxon of MERS-CoV, placing the MERS-CoV root between a recently described virus from African camels and all other viruses. This suggests a higher level of viral diversity in camels than in humans. Together with serologic evidence for widespread MERS-CoV infection in camelids sampled up to 20 years ago in Africa and the Arabian Peninsula, the genetic data indicate that camels act as sources of virus for humans rather than vice versa. The majority of camels on the Arabian Peninsula is imported from the Greater Horn of Africa, where several Neoromicia species occur. The acquisition of MERS-CoV by camels from bats might have taken place in sub-Saharan Africa. Camelids may represent mixing vessels for MERS-CoV and other mammalian CoVs. ⋯ It is unclear how, when, and where the highly pathogenic MERS-CoV emerged. We characterized the full genome of an African bat virus closely related to MERS-CoV and show that human, camel, and bat viruses belong to the same viral species. The bat virus roots the phylogenetic tree of MERS-CoV, providing evidence for an evolution of MERS-CoV in camels that preceded that in humans. The revised tree suggests that humans are infected by camels rather than vice versa. Although MERS-CoV cases occur mainly on the Arabian Peninsula, the data from this study together with serologic and molecular investigations of African camels indicate that the initial host switch from bats may have taken place in Africa. The emergence of MERS-CoV likely involved exchanges of genetic elements between different viral ancestors. These exchanges may have taken place either in bat ancestors or in camels acting as mixing vessels for viruses from different hosts.
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Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes acute fever and acute and chronic musculoskeletal pain in humans. Since 2004, CHIKV has caused millions of cases of disease in the Indian Ocean region and has emerged in new areas, including Europe, the Middle East, and the Pacific region. The mosquito vectors for this virus are globally distributed in tropical and temperate zones, providing the opportunity for CHIKV to continue to expand into new geographic regions. ⋯ In just 9 months, CHIKV has spread to 22 countries in the Caribbean and Central and South America, resulting in hundreds of thousands of cases. CHIKV disease can be highly debilitating, and large epidemics have severe economic consequences. Thus, there is an urgent need for continued research into the epidemiology, pathogenesis, prevention, and treatment of these infections.
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Journal of virology · Oct 2014
Virome analysis of Amblyomma americanum, Dermacentor variabilis, and Ixodes scapularis ticks reveals novel highly divergent vertebrate and invertebrate viruses.
A wide range of bacterial pathogens have been identified in ticks, yet the diversity of viruses in ticks is largely unexplored. In the United States, Amblyomma americanum, Dermacentor variabilis, and Ixodes scapularis are among the principal tick species associated with pathogen transmission. We used high-throughput sequencing to characterize the viromes of these tick species and identified the presence of Powassan virus and eight novel viruses. These included the most divergent nairovirus described to date, two new clades of tick-borne phleboviruses, a mononegavirus, and viruses with similarity to plant and insect viruses. Our analysis revealed that ticks are reservoirs for a wide range of viruses and suggests that discovery and characterization of tick-borne viruses will have implications for viral taxonomy and may provide insight into tick-transmitted diseases. ⋯ Ticks are implicated as vectors of a wide array of human and animal pathogens. To better understand the extent of tick-borne diseases, it is crucial to uncover the full range of microbial agents associated with ticks. Our current knowledge of the diversity of tick-associated viruses is limited, in part due to the lack of investigation of tick viromes. In this study, we examined the viromes of three tick species from the United States. We found that ticks are hosts to highly divergent viruses across several taxa, including ones previously associated with human disease. Our data underscore the diversity of tick-associated viruses and provide the foundation for further studies into viral etiology of tick-borne diseases.
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Journal of virology · Oct 2014
Virus-specific memory CD8 T cells provide substantial protection from lethal severe acute respiratory syndrome coronavirus infection.
Severe acute respiratory syndrome coronavirus (SARS-CoV) caused an acute human respiratory illness with high morbidity and mortality in 2002-2003. Several studies have demonstrated the role of neutralizing antibodies induced by the spike (S) glycoprotein in protecting susceptible hosts from lethal infection. However, the anti-SARS-CoV antibody response is short-lived in patients who have recovered from SARS, making it critical to develop additional vaccine strategies. SARS-CoV-specific memory CD8 T cells persisted for up to 6 years after SARS-CoV infection, a time at which memory B cells and antivirus antibodies were undetectable in individuals who had recovered from SARS. In this study, we assessed the ability of virus-specific memory CD8 T cells to mediate protection against infection in the absence of SARS-CoV-specific memory CD4 T or B cells. We demonstrate that memory CD8 T cells specific for a single immunodominant epitope (S436 or S525) substantially protected 8- to 10-month-old mice from lethal SARS-CoV infection. Intravenous immunization with peptide-loaded dendritic cells (DCs) followed by intranasal boosting with recombinant vaccinia virus (rVV) encoding S436 or S525 resulted in accumulation of virus-specific memory CD8 T cells in bronchoalveolar lavage fluid (BAL), lungs, and spleen. Upon challenge with a lethal dose of SARS-CoV, virus-specific memory CD8 T cells efficiently produced multiple effector cytokines (gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α], and interleukin 2 [IL-2]) and cytolytic molecules (granzyme B) and reduced lung viral loads. Overall, our results show that SARS-CoV-specific memory CD8 T cells protect susceptible hosts from lethal SARS-CoV infection, but they also suggest that SARS-CoV-specific CD4 T cell and antibody responses are necessary for complete protection. ⋯ Virus-specific CD8 T cells are required for pathogen clearance following primary SARS-CoV infection. However, the role of SARS-CoV-specific memory CD8 T cells in mediating protection after SARS-CoV challenge has not been previously investigated. In this study, using a prime-boost immunization approach, we showed that virus-specific CD8 T cells protect susceptible 8- to 10-month-old mice from lethal SARS-CoV challenge. Thus, future vaccines against emerging coronaviruses should emphasize the generation of a memory CD8 T cell response for optimal protection.