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Human hemorrhagic Fever causing arenaviruses: molecular mechanisms contributing to virus virulence and disease pathogenesis.

Shao J, Liang Y, Ly H - Pathogens (2015)

Bottom Line: Why some arenaviruses can cause virulent human infections while others cannot, even though they are isolated from the same rodent hosts, is an enigma.Recent studies have revealed several potential pathogenic mechanisms of arenaviruses, including factors that increase viral replication capacity and suppress host innate immunity, which leads to high viremia and generalized immune suppression as the hallmarks of severe and lethal arenaviral HF diseases.Knowledge gained from these studies can be applied towards the development of novel therapeutics and vaccines against these deadly human pathogens.

View Article: PubMed Central - PubMed

Affiliation: Department of Veterinary and Biomedical Sciences, University of Minnesota, 1988 Fitch Ave., Ste 295, Saint Paul, MN 55108, USA. jshao@umn.edu.

ABSTRACT
Arenaviruses include multiple human pathogens ranging from the low-risk lymphocytic choriomeningitis virus (LCMV) to highly virulent hemorrhagic fever (HF) causing viruses such as Lassa (LASV), Junin (JUNV), Machupo (MACV), Lujo (LUJV), Sabia (SABV), Guanarito (GTOV), and Chapare (CHPV), for which there are limited preventative and therapeutic measures. Why some arenaviruses can cause virulent human infections while others cannot, even though they are isolated from the same rodent hosts, is an enigma. Recent studies have revealed several potential pathogenic mechanisms of arenaviruses, including factors that increase viral replication capacity and suppress host innate immunity, which leads to high viremia and generalized immune suppression as the hallmarks of severe and lethal arenaviral HF diseases. This review summarizes current knowledge of the roles of each of the four viral proteins and some known cellular factors in the pathogenesis of arenaviral HF as well as of some human primary cell-culture and animal models that lend themselves to studying arenavirus-induced HF disease pathogenesis. Knowledge gained from these studies can be applied towards the development of novel therapeutics and vaccines against these deadly human pathogens.

No MeSH data available.


Related in: MedlinePlus

Arenavirus life cycle. 1. Cellular entry is mediated by different cellular receptors (αDG for OW and NW clade C arenaviruses; TfR1 for NW Clade B). Entry of some viruses (e.g., LASV) may also involve a pH-dependent switch to an intracellular receptor (LAMP1) located in the lysosomes. 2. Virus uptake into cells is mediated by endocytosis (OW arenaviruses: clathrin-independent, NW: clathrin-dependent). 3. Virus fusion occurs with the late endosome. 4. Viral RNP is released into the cytoplasm via a pH-dependent membrane fusion mechanism. 5. Viral genome replication, transcription, and protein expression strictly occur in the cytoplasm. 6. Virion assembly and budding occur at the plasma membrane.
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pathogens-04-00283-f003: Arenavirus life cycle. 1. Cellular entry is mediated by different cellular receptors (αDG for OW and NW clade C arenaviruses; TfR1 for NW Clade B). Entry of some viruses (e.g., LASV) may also involve a pH-dependent switch to an intracellular receptor (LAMP1) located in the lysosomes. 2. Virus uptake into cells is mediated by endocytosis (OW arenaviruses: clathrin-independent, NW: clathrin-dependent). 3. Virus fusion occurs with the late endosome. 4. Viral RNP is released into the cytoplasm via a pH-dependent membrane fusion mechanism. 5. Viral genome replication, transcription, and protein expression strictly occur in the cytoplasm. 6. Virion assembly and budding occur at the plasma membrane.

Mentions: The life cycle of arenaviruses starts with virus attachment and entry into cells (Figure 3). The OW and NW clade C arenaviruses use α-dystroglycan (αDG) as their primary receptor [29,30]. Dystroglycan is a ubiquitously expressed glycoprotein that links cells to the extracellular matrix (ECM). It contains two non-covalently associated subunits, αDG and βDG, which play different roles in virus attachment and cellular function. αDG is an extracellular subunit that associates with ECM proteins such as laminin, agrin, perlecan, and neurxins. Upon virus infection, the viral glycoprotein 1 subunit (GP1) mediates attachment to the αDG, which allows the viral particles to internalize and deliver to the late endosomes. βDG is a transmembrane protein that binds to the cytoskeletal adaptor proteins and signaling molecules, but is not required for arenaviral binding and infection [31].


Human hemorrhagic Fever causing arenaviruses: molecular mechanisms contributing to virus virulence and disease pathogenesis.

Shao J, Liang Y, Ly H - Pathogens (2015)

Arenavirus life cycle. 1. Cellular entry is mediated by different cellular receptors (αDG for OW and NW clade C arenaviruses; TfR1 for NW Clade B). Entry of some viruses (e.g., LASV) may also involve a pH-dependent switch to an intracellular receptor (LAMP1) located in the lysosomes. 2. Virus uptake into cells is mediated by endocytosis (OW arenaviruses: clathrin-independent, NW: clathrin-dependent). 3. Virus fusion occurs with the late endosome. 4. Viral RNP is released into the cytoplasm via a pH-dependent membrane fusion mechanism. 5. Viral genome replication, transcription, and protein expression strictly occur in the cytoplasm. 6. Virion assembly and budding occur at the plasma membrane.
© Copyright Policy
Related In: Results  -  Collection

License
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getmorefigures.php?uid=PMC4493475&req=5

pathogens-04-00283-f003: Arenavirus life cycle. 1. Cellular entry is mediated by different cellular receptors (αDG for OW and NW clade C arenaviruses; TfR1 for NW Clade B). Entry of some viruses (e.g., LASV) may also involve a pH-dependent switch to an intracellular receptor (LAMP1) located in the lysosomes. 2. Virus uptake into cells is mediated by endocytosis (OW arenaviruses: clathrin-independent, NW: clathrin-dependent). 3. Virus fusion occurs with the late endosome. 4. Viral RNP is released into the cytoplasm via a pH-dependent membrane fusion mechanism. 5. Viral genome replication, transcription, and protein expression strictly occur in the cytoplasm. 6. Virion assembly and budding occur at the plasma membrane.
Mentions: The life cycle of arenaviruses starts with virus attachment and entry into cells (Figure 3). The OW and NW clade C arenaviruses use α-dystroglycan (αDG) as their primary receptor [29,30]. Dystroglycan is a ubiquitously expressed glycoprotein that links cells to the extracellular matrix (ECM). It contains two non-covalently associated subunits, αDG and βDG, which play different roles in virus attachment and cellular function. αDG is an extracellular subunit that associates with ECM proteins such as laminin, agrin, perlecan, and neurxins. Upon virus infection, the viral glycoprotein 1 subunit (GP1) mediates attachment to the αDG, which allows the viral particles to internalize and deliver to the late endosomes. βDG is a transmembrane protein that binds to the cytoskeletal adaptor proteins and signaling molecules, but is not required for arenaviral binding and infection [31].

Bottom Line: Why some arenaviruses can cause virulent human infections while others cannot, even though they are isolated from the same rodent hosts, is an enigma.Recent studies have revealed several potential pathogenic mechanisms of arenaviruses, including factors that increase viral replication capacity and suppress host innate immunity, which leads to high viremia and generalized immune suppression as the hallmarks of severe and lethal arenaviral HF diseases.Knowledge gained from these studies can be applied towards the development of novel therapeutics and vaccines against these deadly human pathogens.

View Article: PubMed Central - PubMed

Affiliation: Department of Veterinary and Biomedical Sciences, University of Minnesota, 1988 Fitch Ave., Ste 295, Saint Paul, MN 55108, USA. jshao@umn.edu.

ABSTRACT
Arenaviruses include multiple human pathogens ranging from the low-risk lymphocytic choriomeningitis virus (LCMV) to highly virulent hemorrhagic fever (HF) causing viruses such as Lassa (LASV), Junin (JUNV), Machupo (MACV), Lujo (LUJV), Sabia (SABV), Guanarito (GTOV), and Chapare (CHPV), for which there are limited preventative and therapeutic measures. Why some arenaviruses can cause virulent human infections while others cannot, even though they are isolated from the same rodent hosts, is an enigma. Recent studies have revealed several potential pathogenic mechanisms of arenaviruses, including factors that increase viral replication capacity and suppress host innate immunity, which leads to high viremia and generalized immune suppression as the hallmarks of severe and lethal arenaviral HF diseases. This review summarizes current knowledge of the roles of each of the four viral proteins and some known cellular factors in the pathogenesis of arenaviral HF as well as of some human primary cell-culture and animal models that lend themselves to studying arenavirus-induced HF disease pathogenesis. Knowledge gained from these studies can be applied towards the development of novel therapeutics and vaccines against these deadly human pathogens.

No MeSH data available.


Related in: MedlinePlus