scholarly journals Virion Background and Efficiency of Virion Incorporation Determine Susceptibility of Simian Immunodeficiency Virus Env-Driven Viral Entry to Inhibition by IFITM Proteins

2016 ◽  
Vol 91 (2) ◽  
Author(s):  
Florian Wrensch ◽  
Markus Hoffmann ◽  
Sabine Gärtner ◽  
Inga Nehlmeier ◽  
Michael Winkler ◽  
...  
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Viral Entry ◽  
Envelope Protein ◽  
Viral Envelope ◽  
Impact Sensitivity ◽  
Published Data ◽  
Viral Envelope Protein ◽  
Virion Incorporation ◽  
Immunodeficiency Virus ◽  
First Time

ABSTRACT Interferon-induced transmembrane proteins (IFITMs) can inhibit the cellular entry of several enveloped viruses, including simian immunodeficiency virus (SIV). The blockade of SIV by IFITMs is isolate specific, raising the question of which parameters impact sensitivity to IFITM. We show that the virion context in which SIV-Env is presented and the efficiency of virion incorporation determine Env susceptibility to inhibition by IFITMs. Thus, determinants other than the nature of the envelope protein can impact the IFITM sensitivity of viral entry. IMPORTANCE The host cell-encoded IFITM proteins can block viral entry and are an important component of the innate defenses against viral infection. However, the determinants controlling whether a virus is susceptible to blockade by IFITM proteins are incompletely understood. Our study shows that the amount of envelope proteins incorporated into virions as well as the nature of the virion particle itself can impact the sensitivity of viral entry to IFITMs. These results show for the first time that determinants other than the viral envelope protein can impact sensitivity to IFITM and have implications for the interpretation of previously published data on inhibition of viruses by IFITM proteins. Moreover, our findings might help to define the mechanism underlying the antiviral activity of IFITM proteins.

scholarly journals The YXXL Sequences of a Transmembrane Protein of Bovine Leukemia Virus Are Required for Viral Entry and Incorporation of Viral Envelope Protein into Virions

1999 ◽  
Vol 73 (2) ◽  
pp. 1293-1301 ◽  
Author(s):  
Kazunori Inabe ◽  
Masako Nishizawa ◽  
Shigeru Tajima ◽  
Kazuyoshi Ikuta ◽  
Yoko Aida
Keyword(s):  
Viral Entry ◽  
Envelope Protein ◽  
Bovine Leukemia Virus ◽  
Leukemia Virus ◽  
Transient Transfection ◽  
Viral Envelope ◽  
Tyrosine Residue ◽  
Wild Type ◽  
Viral Envelope Protein

ABSTRACT The cytoplasmic domain of an envelope transmembrane glycoprotein (gp30) of bovine leukemia virus (BLV) has two overlapping copies of the (YXXL)2 motif. The N-terminal motif has been implicated in in vitro signal transduction pathways from the external to the intracellular compartment and is also involved in infection and maintenance of high viral loads in sheep that have been experimentally infected with BLV. To determine the role of YXXL sequences in the replication of BLV in vitro, we changed the tyrosine or leucine residues of the N-terminal motif in an infectious molecular clone of BLV, pBLV-IF, to alanine to produce mutated proviruses designated Y487A, L490A, Y498A, L501A, and Y487/498A. Transient transfection of African green monkey kidney COS-1 cells with proviral DNAs that encoded wild-type and mutant sequences revealed that all of the mutated proviral DNAs synthesized mature envelope proteins and released virus particles into the growth medium. However, serial passages of fetal lamb kidney (FLK) cells, which are sensitive to infection with BLV, after transient transfection revealed that mutation of a second tyrosine residue in the N-terminal motif completely prevented the propagation of the virus. Similarly, Y498A and Y487/498A mutant BLV that was produced by the stably transfected COS-1 cells exhibited significantly reduced levels of cell-free virion-mediated transmission. Analysis of the protein compositions of mutant viruses demonstrated that lower levels of envelope protein were incorporated by two of the mutant virions than by wild-type and other mutant virions. Furthermore, a mutation of a second tyrosine residue decreased the specific binding of BLV particles to FLK cells and the capacity for viral penetration. Our data indicate that the YXXL sequences play critical roles in both viral entry and the incorporation of viral envelope protein into the virion during the life cycle of BLV.

scholarly journals West Nile Virus Mosquito Vectors (Diptera: Culicidae) in Germany

Viruses ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 493 ◽  
Author(s):  
Helge Kampen ◽  
Cora M. Holicki ◽  
Ute Ziegler ◽  
Martin H. Groschup ◽  
Birke Andrea Tews ◽  
...  
Keyword(s):  
West Nile Virus ◽  
Virus Strain ◽  
Envelope Protein ◽  
Protein Gene ◽  
Viral Envelope ◽  
Mosquito Vectors ◽  
Viral Envelope Protein ◽  
West Nile ◽  
Qrt Pcr ◽  
First Time

In 2018, West Nile virus (WNV) broke out for the first time in Germany, with continuation of the epidemic in 2019, involving birds, horses and humans. To identify vectors and characterize the virus, mosquitoes were collected in both years in zoological gardens and on a horse meadow immediately following the diagnosis of disease cases in birds and horses. Mosquitoes were identified and screened for WNV by qRT-PCR, with virus-positive samples being sequenced for the viral envelope protein gene. While no positive mosquitoes were found in 2018, seven mosquito pools tested positive for WNV in 2019 in the Tierpark (Wildlife Park) Berlin. The pools consisted of Cx. pipiens biotype pipiens (n = 5), and a mixture of Cx. p. biotype pipiens and Cx. p. biotype molestus (n = 2), or hybrids of these, and were collected between 13 August and 24 September 2019. The virus strain turned out to be nearly identical to two WNV strains isolated from birds diseased in 2018 in eastern Germany. The findings represent the first demonstration of WNV in mosquitoes in Germany and include the possibility of local overwintering of the virus.

An immunoelectron microscopy investigation of simian immunodeficiency virus (SIV) infected AA2 cells

1992 ◽  
Vol 50 (1) ◽  
pp. 814-815
Author(s):  
W.N. Norton ◽  
C.R. Brown ◽  
M.K. Rippy ◽  
M. Lewis ◽  
P.M. Zack
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Clinical Manifestations ◽  
Receptor Site ◽  
Initial Step ◽  
Viral Envelope ◽  
Viral Envelope Protein ◽  
Microscopy Investigation ◽  
Immunodeficiency Virus ◽  
Siv Infection ◽  
Envelope Protein Gp120

Human immunodeficiency virus (HIV), the causative agent of AIDS, and simian immunodeficiency virus (SIV) are both retroviruses and members of the lentivirus family. The initial step leading to infection for HIV and SIV involves the binding of a viral envelope protein, GP120, to a specific surface determinate, CD4, which serves as a receptor site. The clinical manifestations of SIV infection in the Asian macaque, an important primate host of the virus, are similar to those detected in humans diagnosed with AIDS. Consequently, SIV and its host represent a potentially valuable system in which drugs and vaccines focused against HIV can be subjected to testing.

scholarly journals A Quantitative Affinity-Profiling System That Reveals Distinct CD4/CCR5 Usage Patterns among Human Immunodeficiency Virus Type 1 and Simian Immunodeficiency Virus Strains

2009 ◽  
Vol 83 (21) ◽  
pp. 11016-11026 ◽  
Author(s):  
Samantha. H. Johnston ◽  
Michael A. Lobritz ◽  
Sandra Nguyen ◽  
Kara Lassen ◽  
Shirley Delair ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Simian Immunodeficiency Virus ◽  
Viral Entry ◽  
Three Dimensional ◽  
Viral Envelope ◽  
Ccr5 Expression ◽  
Immunodeficiency Virus ◽  
Ccr5 Usage ◽  
Entry Efficiency

ABSTRACT The affinity of human immunodeficiency virus (HIV) envelope for CD4 and CCR5 appears to be associated with aspects of R5 virus (virus using the CCR5 coreceptor) pathogenicity. However, entry efficiency results from complex interactions between the viral envelope glycoprotein and both CD4 and CCR5, which limits attempts to correlate viral pathogenicity with surrogate measures of envelope CD4 and CCR5 affinities. Here, we present a system that provides a quantitative and comprehensive characterization of viral entry efficiency as a direct interdependent function of both CD4 and CCR5 levels. This receptor affinity profiling system also revealed heretofore unappreciated complexities underlying CD4/CCR5 usage. We first developed a dually inducible cell line in which CD4 and CCR5 could be simultaneously and independently regulated within a physiologic range of surface expression. Infection by multiple HIV type 1 (HIV-1) and simian immunodeficiency virus isolates could be examined simultaneously for up to 48 different combinations of CD4/CCR5 expression levels, resulting in a distinct usage pattern for each virus. Thus, each virus generated a unique three-dimensional surface plot in which viral infectivity varied as a function of both CD4 and CCR5 expression. From this functional form, we obtained a sensitivity vector along with corresponding metrics that quantified an isolate's overall efficiency of CD4/CCR5 usage. When applied to viral isolates with well-characterized sensitivities to entry/fusion inhibitors, the vector metrics were able to encapsulate their known biological phenotypes. The application of the vector metrics also indicated that envelopes derived from elite suppressors had overall-reduced entry efficiencies compared to those of envelopes derived from chronically infected viremic progressors. Our affinity-profiling system may help to refine studies of R5 virus tropism and pathogenesis.

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