Utilization of human DC-SIGN and L-SIGN for entry and infection of host cells by the New World arenavirus, Junín virus

Martínez, María del Carmen Jiménez; Bialecki, Michele A.; Belouzard, Sandrine; Cordo, Sandra M.; Candurra, Nélida A.; Whittaker, Gary R.

doi:10.1016/j.bbrc.2013.10.106

Cited by 32 publications

(25 citation statements)

References 32 publications

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“…1A. Therefore, we decided to further explore this observation by performing a time course infection (2,6,9,12, and 24 h of infection) followed by Western blot analysis of LC3-II. In order to do this, monolayers of A549 cells were infected with JUNV at an MOI of 1, and monoclonal antibodies against JUNV nucleoprotein, which specifically recognize JUNV NP, were employed to estimate the infection progress.…”

mentioning

confidence: 99%

Junín Virus Promotes Autophagy To Facilitate the Virus Life Cycle

Roldan

Candurra

Colombo

et al. 2019

J Virol

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Junín virus (JUNV), a member of the family Arenaviridae, is the etiological agent of Argentine hemorrhagic fever (AHF), a potentially deadly endemicepidemic disease affecting the population of the most fertile farming land of Argentina. Autophagy is a degradative process with a crucial antiviral role; however, several viruses subvert the pathway to their benefit. We determined the role of autophagy in JUNV-infected cells by analyzing LC3, a cytoplasmic protein (LC3-I) that becomes vesicle membrane associated (LC3-II) upon induction of autophagy. Cells overexpressing enhanced green fluorescent protein (EGFP)-LC3 and infected with JUNV showed an increased number of LC3 punctate structures, similar to those obtained after starvation or bafilomycin A1 treatment, which leads to autophagosome induction or accumulation, respectively. We also monitored the conversion of LC3-I to LC3-II, observing LC3-II levels in JUNV-infected cells similar to those observed in starved cells. Additionally, we kinetically studied the number of LC3 dots after JUNV infection and found that the virus activated the pathway as early as 2 h postinfection (p.i.), whereas the UV-inactivated virus did not induce the pathway. Cells subjected to starvation or pretreated with rapamycin, a pharmacological autophagy inductor, enhanced virus yield. Also, we assayed the replication capacity of JUNV in Atg5 knockout or Beclin 1 knockdown cells (both critical components of the autophagic pathway) and found a significant decrease in JUNV replication. Taken together, our results constitute the first study indicating that JUNV infection induces an autophagic response, which is functionally required by the virus for efficient propagation. IMPORTANCE Mammalian arenaviruses are zoonotic viruses that cause asymptomatic and persistent infections in their rodent hosts but may produce severe and lethal hemorrhagic fevers in humans. Currently, there are neither effective therapeutic options nor effective vaccines for viral hemorrhagic fevers caused by humanpathogenic arenaviruses, except the vaccine Candid no. 1 against Argentine hemorrhagic fever (AHF), licensed for human use in areas of endemicity in Argentina. Since arenaviruses remain a severe threat to global public health, more in-depth knowledge of their replication mechanisms would improve our ability to fight these viruses. Autophagy is a lysosomal degradative pathway involved in maintaining cellular homeostasis, representing powerful anti-infective machinery. We show, for the first time for a member of the family Arenaviridae, a proviral role of autophagy in JUNV infection, providing new knowledge in the field of host-virus interaction. Therefore, modulation of virus-induced autophagy could be used as a strategy to block arenavirus infections.

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confidence: 99%

Junín Virus Promotes Autophagy To Facilitate the Virus Life Cycle

Roldan

Candurra

Colombo

et al. 2019

J Virol

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“…7B) and infected with WWAV, AV96010151, BBTV, JUNV, or VSV pseudovirus. The low level of entry by arenaviruses in the mock-transduced NIH 3T3 cells might indicate their ability to use phosphatidylserine receptors, C-type lectins (40,41), or other similar molecules that are expressed in these cells. As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Human and Host Species Transferrin Receptor 1 Use by North American Arenaviruses

Zong

Fofana

Choe

2014

J Virol

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At least five New World (NW) arenaviruses cause hemorrhagic fevers in South America. These pathogenic clade B viruses, as well as nonpathogenic arenaviruses of the same clade, use transferrin receptor 1 (TfR1) of their host species to enter cells. Pathogenic viruses are distinguished from closely related nonpathogenic ones by their additional ability to utilize human TfR1 (hTfR1). Here, we investigate the receptor usage of North American arenaviruses, whose entry proteins share greatest similarity with those of the clade B viruses. We show that all six North American arenaviruses investigated utilize host species TfR1 orthologs and present evidence consistent with arenavirus-mediated selection pressure on the TfR1 of the North American arenavirus host species. Notably, one of these viruses, AV96010151, closely related to the prototype Whitewater Arroyo virus (WWAV), entered cells using hTfR1, consistent with a role for a WWAV-like virus in three fatal human infections whose causative agent has not been identified. In addition, modest changes were sufficient to convert hTfR1 into a functional receptor for most of these viruses, suggesting that a minor alteration in virus entry protein may allow these viruses to use hTfR1. Our data establish TfR1 as a cellular receptor for North American arenaviruses, highlight an "arms race" between these viruses and their host species, support the association of North American arenavirus with fatal human infections, and suggest that these viruses have a higher potential to emerge and cause human diseases than has previously been appreciated. IMPORTANCEhTfR1 use is a key determinant for a NW arenavirus to cause hemorrhagic fevers in humans. All known pathogenic NW arenaviruses are transmitted in South America by their host rodents. North American arenaviruses are generally considered nonpathogenic, but some of these viruses have been tentatively implicated in human fatalities. We show that these North American arenaviruses use the TfR1 orthologs of their rodent host species and identify TfR1 polymorphisms suggesting an ongoing "arms race" between these viruses and their hosts. We also show that a close relative of a North American arenavirus suggested to have caused human fatalities, the Whitewater Arroyo species complex virus AV96010151, uses human TfR1. Moreover, we present data that imply that modest changes in other North American arenaviruses might allow these viruses to infect humans. Collectively, our data suggest that North American arenaviruses have a higher potential to cause human disease than previously assumed.

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“…Soluble hTfR1 or the monocolonal antibody ch128.1, which is specific for hTfR1, could also be considered as they are known to block entry of JUNV into cells 13,36 . Additionally, pretreatment of cells with free mannose 14 or incubation of particles with JUNV-specific neutralizing antibodies 37 can inhibit virus entry.…”

Section: Carry Out Virus-cell Attachmentmentioning

confidence: 99%

“…The L and S genomic RNA segments (vRNAs) are packaged into virions [10][11][12] . The initial step of arenavirus infection is attachment of viral particles to host cells through an interaction between the viral GP and its corresponding host cell receptors which, for JUNV, includes the human transferrin receptor 1 (hTfR1) 13,14 . Following attachment, JUNV particles are taken into the cell via clathrin-mediated endocytosis 15 .…”

Section: Introductionmentioning

confidence: 99%

Highly Sensitive Assay for Measurement of Arenavirus-cell Attachment

Klaus

Botten

2016

JoVE

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Arenaviruses are a family of enveloped RNA viruses that cause severe human disease. The first step in the arenavirus life cycle is attachment of viral particles to host cells. While virus-cell attachment can be measured through the use of virions labeled with biotin, radioactive isotopes, or fluorescent dyes, these approaches typically require high multiplicities of infection (MOI) to enable detection of bound virus. We describe a quantitative (q)RT-PCR-based assay that measures Junin virus strain Candid 1 attachment via quantitation of virion-packaged viral genomic RNA. This assay has several advantages including its extreme sensitivity and ability to measure attachment over a large dynamic range of MOIs without the need to purify or label input virus. Importantly, this approach can be easily tailored for use with other viruses through the use of virus-specific qRT-PCR reagents. Further, this assay can be modified to permit measurement of particle endocytosis and genome uncoating. In conclusion, we describe a simple, yet robust assay for highly sensitive measurement of arenavirus-cell attachment.

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Utilization of human DC-SIGN and L-SIGN for entry and infection of host cells by the New World arenavirus, Junín virus

Cited by 32 publications

References 32 publications

Junín Virus Promotes Autophagy To Facilitate the Virus Life Cycle

Junín Virus Promotes Autophagy To Facilitate the Virus Life Cycle

Human and Host Species Transferrin Receptor 1 Use by North American Arenaviruses

Highly Sensitive Assay for Measurement of Arenavirus-cell Attachment

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