scholarly journals Mice Transgenic for a Human Porcine Endogenous Retrovirus Receptor Are Susceptible to Productive Viral Infection

2006 ◽  
Vol 80 (7) ◽  
pp. 3135-3146 ◽  
Author(s):  
Y. Martina ◽  
K. T. Marcucci ◽  
S. Cherqui ◽  
A. Szabo ◽  
T. Drysdale ◽  
...  

ABSTRACT Porcine endogenous retrovirus (PERV) is considered one of the major risks in xenotransplantation. No valid animal model has been established to evaluate the risks associated with PERV transmission to human patients by pig tissue xenotransplantation or to study the potential pathogenesis associated with PERV infection. In previous work we isolated two genes encoding functional human PERV receptors and proved that introduction of these into mouse fibroblasts allowed the normally nonpermissive mouse cells to become productively infected (T. A. Ericsson, Y. Takeuchi, C. Templin, G. Quinn, S. F. Farhadian, J. C. Wood, B. A. Oldmixon, K. M. Suling, J. K. Ishii, Y. Kitagawa, T. Miyazawa, D. R. Salomon, R. A. Weiss, and C. Patience, Proc. Natl. Acad. Sci. USA 100:6759-6764, 2003). In the present study we created mice transgenic for human PERV-A receptor 2 (HuPAR-2). After inoculation of transgenic animals with infectious PERV supernatants, viral DNA and RNA were detected at multiple time points, indicating productive replication. This establishes the role of HuPAR-2 in PERV infection in vivo; in addition, these transgenic mice represent a new model for determining the risk of PERV transmission and potential pathogenesis. These mice also create a unique opportunity to study the immune response to PERV infection and test potential therapeutic or preventative modalities.

2006 ◽  
Vol 38 (7) ◽  
pp. 2261-2263 ◽  
Author(s):  
Z. Li ◽  
Y. Ping ◽  
L. Shengfu ◽  
L. Youping ◽  
C. Jingqiu ◽  
...  

2001 ◽  
Vol 72 (12) ◽  
pp. 1996-2000 ◽  
Author(s):  
Gillian A. Langford ◽  
Daniel Galbraith ◽  
Alison J. Whittam ◽  
Paul McEwan ◽  
Xos?? M. Fern??ndez-Su??rez ◽  
...  

2005 ◽  
Vol 12 (4) ◽  
pp. 286-292 ◽  
Author(s):  
Giuseppe Di Nicuolo ◽  
Maarten-Paul Kerkhove ◽  
Ruurdtje Hoekstra ◽  
Marcel G. H. M. Beld ◽  
Pietro Amoroso ◽  
...  

Blood ◽  
2008 ◽  
Vol 112 (10) ◽  
pp. 4284-4291 ◽  
Author(s):  
Robert M. Cohen ◽  
Robert S. Franco ◽  
Paramjit K. Khera ◽  
Eric P. Smith ◽  
Christopher J. Lindsell ◽  
...  

AbstractAlthough red blood cell (RBC) life span is a known determinant of percentage hemoglobin A1c (HbA1c), its variation has been considered insufficient to affect clinical decisions in hematologically normal persons. However, an unexplained discordance between HbA1c and other measures of glycemic control can be observed that could be, in part, the result of differences in RBC life span. To explore the hypothesis that variation in RBC life span could alter measured HbA1c sufficiently to explain some of this discordance, we determined RBC life span using a biotin label in 6 people with diabetes and 6 nondiabetic controls. Mean RBC age was calculated from the RBC survival curve for all circulating RBCs and for labeled RBCs at multiple time points as they aged. In addition, HbA1c in magnetically isolated labeled RBCs and in isolated transferrin receptor-positivereticulocytes was used to determine the in vivo synthetic rate of HbA1c. The mean age of circulating RBCs ranged from 39 to 56 days in diabetic subjects and 38 to 60 days in nondiabetic controls. HbA1c synthesis was linear and correlated with mean whole blood HbA1c (R2 = 0.91). The observed variation in RBC survival was large enough to cause clinically important differences in HbA1c for a given mean blood glucose.


2003 ◽  
Vol 64 (7) ◽  
pp. 708-717 ◽  
Author(s):  
Brice W McKane ◽  
Sabarinathan Ramachandran ◽  
Junbao Yang ◽  
Xiao-Chun Xu ◽  
T Mohanakumar

2018 ◽  
Vol 3 ◽  
pp. 25 ◽  
Author(s):  
Rachel J. Skilton ◽  
Yibing Wang ◽  
Colette O'Neill ◽  
Simone Filardo ◽  
Peter Marsh ◽  
...  

Background:Research in chlamydial genetics is challenging because of its obligate intracellular developmental cycle.In vivosystems exist that allow studies of different aspects of basic biology of chlamydiae, the murineChlamydia muridarummodel is one of great importance and thus an essential research tool.C. muridarumcarries a plasmid that has a role in virulence.  Our aim was to compare and contrast theC. muridarumplasmid-free phenotype with that of a chromosomally isogenic plasmid-bearing strain, through the inclusion phase of the developmental cycle.Methods:We measured infectivity for plasmid bearing and plasmid-curedC. muridarumby inclusion forming assays in McCoy cells and in parallel bacterial chromosome replication by quantitative PCR, throughout the developmental cycle. In addition to these studies, we have carefully monitored chlamydial inclusion formation by confocal microscopy and transmission electron microscopy. A newE.coli/chlamydial shuttle vector (pNigg::GFP) was constructed using standard cloning technology and used to transformC. muridarumfor further phenotypic studies.Results:We have advanced the definition of the chlamydial phenotype away from the simple static observation of mature inclusions and redefined theC. muridarumplasmid-based phenotype on growth profile and inclusion morphology. Our observations on the growth properties of plasmid-curedC. muridarumchallenge the established interpretations, especially with regard to inclusion growth kinetics. Introduction of the shuttle plasmid pNigg::GFP into plasmid-curedC. muridarumrestored the wild-type plasmid-bearing phenotype and confirmed that loss of the plasmid was the sole cause for the changes in growth and chromosomal replication.Conclusions:Accurate growth curves and sampling at multiple time points throughout the developmental cycle is necessary to define plasmid phenotypes.  There are subtle but important (previously unnoticed) differences in the overall growth profile of plasmid-bearing and plasmid-freeC. muridarum.  We have proven that the differences described are solely due to the plasmid pNigg.


2000 ◽  
Vol 74 (18) ◽  
pp. 8575-8581 ◽  
Author(s):  
Steffi Bösch ◽  
Claire Arnauld ◽  
André Jestin

ABSTRACT Specific-pathogen-free (SPF) swine appear to be the most appropriate candidate for pig to human xenotransplantation. Still, the risk of endogenous retrovirus transmission represents a major obstacle, since two human-tropic porcine endogenous retroviruses (PERVs) had been characterized in vitro (P. Le Tissier, J. P. Stoye, Y. Takeuchi, C. Patience, and R. A. Weiss, Nature 389:681–682, 1997). Here we addressed the question of PERV distribution in a French Large White SPF pig herd in vivo. First, PCR screening for previously described PERV envelope genes envA, envB, and envC(D. E. Akiyoshi, M. Denaro, H. Zhu, J. L. Greenstein, P. Banerjee, and J. A. Fishman, J. Virol. 72:4503–4507, 1998; Le Tissier et al., op. cit.). demonstrated ubiquity of envAand envB sequences, whereas envC genes were absent in some animals. On this basis, selective out-breeding of pigs of remote origin might be a means to reduce proviral load in organ donors. Second, we investigated PERV genome carriage inenvC negative swine. Eleven distinct full-length PERV transcripts were isolated. The sequence of the complete envelope open reading frame was determined. The deduced amino acid sequences revealed the existence of four clones with functional and five clones with defective PERV PK-15 A- and B-like envelope sequences. The occurrence of easily detectable levels of PERV variants in different pig tissues in vivo heightens the need to assess PERV transmission in xenotransplantation animal models.


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