Avid Bioservices Inc (CDMO)

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Recent paper on PS receptors, PS and viruses in PLOS Pathogens, March 2013.
Open access:
http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1003232
TIM-family Proteins Promote Infection of Multiple Enveloped Viruses through Virion-associated Phosphatidylserine
Stephanie Jemielity 1, Jinyize J. Wang 1, Ying Kai Chan 2, Asim A. Ahmed 1, Wenhui Li 3, Sheena Monahan 4,
Xia Bu 5, Michael Farzan 2¤, Gordon J. Freeman 5, Dale T. Umetsu 4, Rosemarie H. DeKruyff 4,
Hyeryun Choe 1¤*
1 Division of Respiratory Diseases Children’s Hospital Boston, Harvard Medical School, Boston, Massachusetts, United States of America, 2 New England Primate Center,
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, United States of America, 3 National Institute of Biological Sciences,
Beijing, China, 4 Division of Immunology, Children’s Hospital Boston, Harvard Medical School, Boston, Massachusetts, United States of America, 5 Department of Medical
Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America
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Some quotes from the paper:
[snip]
Several recent findings suggest that negatively-charged phospholipids
like PS might play a role in mediating virus entry. PS was
shown to be exposed on the membranes of various enveloped
viruses, including Pichinde virus, vesicular stomatitis virus (VSV)
and the intracellular mature virion form of Vaccinia virus [32,33].
This is likely a common feature of most enveloped viruses, as virusinfected
cells were shown to overexpress PS on their plasma
membranes [32–34]. In addition, the entry of lentiviral pseudoviruses
bearing the GPs of Sindbis (SINV), Ross River (RRV) and
Baculo virus was enhanced in a PS-dependent manner by the
TAM receptor tyrosine kinase Axl [35]. Axl has also been shown
to promote EBOV and MARV entry [11]. Finally, an antibody
targeting anionic phospholipids effectively rescued rodents from
lethal challenges by either Pichinde virus or mouse cytomegalovirus,
demonstrating in vivo contribution of anionic phospholipids
to the infectivity of these viruses [33].
[snip]
PS receptors form a complementary, widely expressed
network of receptors that is characterized by functional rather
than structural conservation. These particular features of PS
receptors likely contribute to their exploitation by viruses as
attachment factors. Notably, several PS receptors, including
TIM4, are highly expressed on mammalian macrophages and
dendritic cells. These cells play critical roles in the initial stages
of infection of filoviruses and flaviviruses in particular [55,56,65],
and PS receptors may thus play correspondingly important roles
in establishing these infections. PS receptors may be more
important still for viruses like DENV, WNV, EEEV and CHKV,
which are borne by insect vectors. The role of PS as apoptotic
marker is conserved in insects [66], and compared to mammalian
cells the membranes of insect cells are generally enriched
with PE [67,68], which binds several PS receptors. Thus
mosquito-delivered virions may especially benefit from PS
receptor-mediated enhancement of infection.
In conclusion, our results indicate that hTIM1, hTIM4, hAxl
and potentially other PS-binding receptors can enhance the entry
of a number of highly divergent viruses. As demonstrated for
hTIM1, the enhancement conferred by all of these receptors is
likely PS dependent and does not require any viral entry protein.
Accordingly, these proteins cannot properly be described as viral
receptors, although the nature of the viral entry protein clearly
impacts the relevance of PS receptors to infection. In some cases,
PS receptors may play critical roles in establishing or maintaining
an in vivo infection, which could affect disease severity. Thus our
results support the proposal of Soares et al., demonstrated for
Pichinde virus and mouse cytomegalovirus [33], that therapeutic
strategies targeting PS and other anionic phospholipids may be
broadly effective against a wide range of viruses.
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Notes:
[33]. Soares MM, King SW, Thorpe PE (2008) Targeting inside-out phosphatidylserine
as a therapeutic strategy for viral diseases. Nat Med 14: 1357–1362.
Gordon Freeman gave a seminar at UTSW, hosted by Dr. Thorpe, at the end of February.