Junín virus (JUNV), the causative agent of Argentine haemorrhagic fever, is a human pathogen that naturally enters the body through the epithelial cells of the respiratory and digestive tracts. The interaction of JUNV with two types of polarized epithelial cultures, Vero C1008 and A549, was investigated. Radioactive virus-binding assays showed that JUNV infects polarized lines preferentially through the apical surface. High-level expression of viral nucleoprotein was detected in polarized cell lines infected through the apical domain. Virus production from apical media was about 100-fold higher than that found into the basolateral medium. Confocal-immunofluorescence analysis revealed high-level expression of glycoprotein at the apical-membrane surface. Disruption of the microtubule network by colchicine impaired JUNV vectorial release. This is the first study to analyse the interaction between a member of the virus family Arenaviridae and polarized epithelial cells, showing preferential entry and release from the apical plasma membrane.
BoseS.,
MalurA.,
BanerjeeA. K.2001; Polarity of human parainfluenza virus type 3 infection in polarized human lung epithelial A549 cells: role of microfilament and microtubule. J Virol 75:1984–1989[CrossRef]
CaoW.,
HenryM. D.,
BorrowP.7 other authors1998; Identification of α -dystroglycan as a receptor for lymphocytic choriomeningitis virus and Lassa fever virus. Science 282:2079–2081[CrossRef]
ChuJ. J. H.,
NgM. L.2002; Infection of polarized epithelial cells with flavivirus West Nile: polarized entry and egress of virus occur though the apical surface. J Gen Virol 83:2427–2435
ClaysonE. T.,
BrandoL. V. J.,
CompansR. W.1989; Release of simian virus 40 virions from epithelial cells is polarized and occurs without cell lysis. J Virol 63:2278–2288
ContigianiM. S.,
SabattiniM. S.1977; Virulencia diferencial de cepas de virus Junín por marcadores Biológicos en ratones y cobayos. Medicina (B Aires) 37:244–251 (in Spanish)
DamonteE. B.,
MersichS. E.,
CandurraN. A.1994; Intracellular processing and transport of Junin virus glycoproteins influences virion infectivity. Virus Res 34:317–326[CrossRef]
FullerS.,
von BonsdorffC.-H.,
SimonsK.1984; Vesicular stomatitis virus infects and matures only through the basolateral surface of the polarized epithelial cell line, MDCK. Cell 38:65–77[CrossRef]
LafontF.,
BurkhardtJ. K.,
SimonsK.1994; Involvement of microtubule motors in basolateral and apical transport in kidney cells. Nature 372:801–803[CrossRef]
LaguensM.,
ChambóJ. G.,
LaguensR. P.1983; In vivo replication of pathogenic and attenuated strains of Junin virus in different cell populations of lymphatic tissue. Infect Immun 41:1279–1283
MarozinS.,
PrankU.,
SodeikB.2004; Herpes simplex virus type 1 infection of polarized epithelial cells requires microtubules and access to receptors present at cell–cell contact sites. J Gen Virol 85:775–786[CrossRef]
NeelyJ. D.,
Amiry-MoghaddamM.,
OttersenO. P.,
FroehnerS. C.,
AgreP.,
AdamsM. E.2001; Syntrophin-dependent expression and localization of Aquaporin-4 water channel protein. Proc Natl Acad Sci U S A 98:14108–14113[CrossRef]
RomanowskiV.1993; Genetic organization of Junín virus, the etiological agent of Argentine hemorrhagic fever. In The Arenaviridae pp 51–83 Edited by
SalvatoM. S.
New York: Plenum;
RossenJ. W. A.,
BekkerC. P. J.,
VoorhoutW. F.,
StrousG. J. A. M.,
van der EndeA.,
RottierP. J. M.1994; Entry and release of transmissible gastroenteritis coronavirus are restricted to apical surfaces of polarized epithelial cells. J Virol 68:7966–7973
ScolaroL. A.,
MersichS. E.,
DamonteE. B.1989; Reduced virulence of a Junin virus mutant is associated with restricted multiplication in murine cells. Virus Res 13:283–294[CrossRef]
SpiropoulouC. F.,
KunzS.,
RollinP. E.,
CampbellK. P.,
OldstoneM. B. A.2002; New World arenavirus clade C, but not clade A and B viruses, utilizes α -dystroglycan as its major receptor. J Virol 76:5140–5146[CrossRef]
ZegersM. M. P.,
ZaalK. J. M.,
van IJzendoornS. C. D.,
KlappeK.,
HoekstraD.1998; Actin filaments and microtubules are involved in different membrane traffic pathways that transport sphingolipids to the apical surface of polarized HepG2 cells. Mol Biol Cell 9:1939–1949[CrossRef]