Abstract
The glycoprotein (GP) of arenaviruses is glycosylated at 11 conserved N-glycosylation sites. We constructed recombinant lymphocytic choriomeningitis virus (rLCMV) featuring either additions or deletions of these N-glycans to investigate their role in the viral life cycle. N-glycosylation at two sites, T87 and S97, were found to be necessary to rescue rLCMV. Three of nine successfully rescued mutants, S116A, T234A, and S373A, under selective pressures in either epithelial, neuronal, or macrophage cells reverted to WT sequence. Of the seven stable N-glycan deletion mutants, five of these led to altered viral fitness and cell tropism, assessed as growth in either mouse primary cortical neurons or bone marrow derived macrophages. These results demonstrate that the deletion of N-glycans in LCMV GP may confer an advantage to the virus for infection of neurons but a disadvantage in macrophages.
Highlights
The Arenaviridae are enveloped bi-segmented single stranded RNA viruses, with 25 species currently being recognized [1,2,3,4]
Desired mutations in the Nglycosylation sites were inserted in the glycoprotein cDNA
We engineered recombinant lymphocytic choriomeningitis virus (rLCMV) with deletion or addition of N-glycans on the WT lymphocytic choriomeningitis virus (LCMV) glycoprotein [41]
Summary
The Arenaviridae are enveloped bi-segmented single stranded RNA viruses, with 25 species currently being recognized [1,2,3,4]. Junın, Machupo, Guanarito, and Sabia viruses are known to cause hemorrhagic fever in West Africa, Argentina, Bolivia, Venezuela, and Brazil, respectively [2,5,6,7,8,9,10,11,12]. The high degree of genetic variation among geographic and temporal isolates of the same arenavirus species supports the concept of continued emergence of new pathogens [20], as recently proven by the identification two novel arenaviruses: Lujo and Dandenong; isolated respectively from a fatal outbreak [3,21] and from fatal organ transplants [22]
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