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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

Arenaviral ambisense-genome replication strategy: due to the ambisense coding strategy of the arenaviruses, the NP (and L) genes are transcribed directly from the viral genomic segments into mRNAs, whereas the GP (and Z) mRNAs must be transcribed from the antigenomic strands after genome replication.
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pathogens-04-00283-f002: Arenaviral ambisense-genome replication strategy: due to the ambisense coding strategy of the arenaviruses, the NP (and L) genes are transcribed directly from the viral genomic segments into mRNAs, whereas the GP (and Z) mRNAs must be transcribed from the antigenomic strands after genome replication.

Mentions: The arenavirus genome is composed of two single-stranded negative-sense RNAs of about 7.2 kb and 3.5 kb (Figure 1). Each genomic segment code for the two proteins is from an opposite orientation, which is known as ambisense coding strategy. The large (L) segment encodes the RNA-dependent RNA polymerase (RdRp) L protein and matrix protein Z. The small (S) segment encodes the nucleoprotein (NP) and glycoprotein precursor (GP) [27]. Arenavirus genomic RNA segments do not serve as a direct template for translation. Due to the ambisense coding strategy (Figure 2), the NP and L mRNAs are transcribed from genomic RNAs, whereas the GP and Z viral mRNA are transcribed from the anti-genomic RNAs. The intergenic region (IGR) separates the two genes on each RNA segment, and the hairpin structure of IGR is believed to provide the termination signal of transcription.


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

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

Arenaviral ambisense-genome replication strategy: due to the ambisense coding strategy of the arenaviruses, the NP (and L) genes are transcribed directly from the viral genomic segments into mRNAs, whereas the GP (and Z) mRNAs must be transcribed from the antigenomic strands after genome replication.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493475&req=5

pathogens-04-00283-f002: Arenaviral ambisense-genome replication strategy: due to the ambisense coding strategy of the arenaviruses, the NP (and L) genes are transcribed directly from the viral genomic segments into mRNAs, whereas the GP (and Z) mRNAs must be transcribed from the antigenomic strands after genome replication.
Mentions: The arenavirus genome is composed of two single-stranded negative-sense RNAs of about 7.2 kb and 3.5 kb (Figure 1). Each genomic segment code for the two proteins is from an opposite orientation, which is known as ambisense coding strategy. The large (L) segment encodes the RNA-dependent RNA polymerase (RdRp) L protein and matrix protein Z. The small (S) segment encodes the nucleoprotein (NP) and glycoprotein precursor (GP) [27]. Arenavirus genomic RNA segments do not serve as a direct template for translation. Due to the ambisense coding strategy (Figure 2), the NP and L mRNAs are transcribed from genomic RNAs, whereas the GP and Z viral mRNA are transcribed from the anti-genomic RNAs. The intergenic region (IGR) separates the two genes on each RNA segment, and the hairpin structure of IGR is believed to provide the termination signal of transcription.

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