Infectious Lassa virus, but not filoviruses, is restricted by BST-2/tetherin.
Bone marrow stromal antigen 2 (BST-2/tetherin) is a cellular membrane protein that inhibits the release of HIV-1. We show for the first time, using infectious viruses, that BST-2 also inhibits egress of arenaviruses but has no effect on filovirus replication and spread. Specifically, infectious Lassa virus (LASV) release significantly decreased or increased in human cells in which BST-2 was either stably expressed or knocked down, respectively. In contrast, replication and spread of infectious Zaire ebolavirus (ZEBOV) and Lake Victoria marburgvirus (MARV) were not affected by these conditions. Replication of infectious Rift Valley fever virus (RVFV) and cowpox virus (CPXV) was also not affected by BST-2 expression. Elevated cellular levels of human or murine BST-2 inhibited the release of virus-like particles (VLPs) consisting of the matrix proteins of multiple highly virulent NIAID Priority Pathogens, including arenaviruses (LASV and Machupo virus [MACV]), filoviruses (ZEBOV and MARV), and paramyxoviruses (Nipah virus). Although the glycoproteins of filoviruses counteracted the antiviral activity of BST-2 in the context of VLPs, they could not rescue arenaviral (LASV and MACV) VLP release upon BST-2 overexpression. Furthermore, we did not observe colocalization of filoviral glycoproteins with BST-2 during infection with authentic viruses. None of the arenavirus-encoded proteins rescued budding of VLPs in the presence of BST-2. Our results demonstrate that BST-2 might be a broad antiviral factor with the ability to restrict release of a wide variety of human pathogens. However, at least filoviruses, RVFV, and CPXV are immune to its inhibitory effect.
Radoshitzky
Sheli R
SR
U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter St., Fort Detrick, Frederick, MD 21702, USA.
Dong
Lian
L
Chi
Xiaoli
X
Clester
Jeremiah C
JC
Retterer
Cary
C
Spurgers
Kevin
K
Kuhn
Jens H
JH
Sandwick
Sarah
S
Ruthel
Gordon
G
Kota
Krishna
K
Boltz
Dutch
D
Warren
Travis
T
Kranzusch
Philip J
PJ
Whelan
Sean P J
SP
Bavari
Sina
S
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D006477:Arenaviruses, New World / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D001483:Base Sequence; D002460:Cell Line; D004279:DNA, Viral / Q000235:genetics; D029043:Ebolavirus / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D016563:Filoviridae / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D058851:GPI-Linked Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D054884:Host-Pathogen Interactions / Q000502:physiology; D006801:Humans; D007836:Lassa virus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D029024:Marburgvirus / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D045405:Nipah Virus / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D034741:RNA, Small Interfering / Q000235:genetics; D014162:Transfection; D057074:Virus Release / Q000502:physiology; D000074010:Bone Marrow Stromal Antigen 2
D015703:Antigens, CD; D004279:DNA, Viral; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; D034741:RNA, Small Interfering; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C513868:BST2 protein, mouse