Characterization of mouse lines transgenic with the human poliovirus receptor gene

Deatly, Anne M.; Taffs, Rolf E.; McAuliffe, Josephine M.; Nawoschik, Stanley; Coleman, John W.; McMullen, Gail; Weeks‐Levy, Carolyn; Johnson, Adriana; Racaniello, Vincent R.

doi:10.1006/mpat.1998.0212

Cited by 13 publications

(18 citation statements)

References 40 publications

(9 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hence, a human transgene inserted into the mouse genome is expected to be chromatinized like an endogenous mouse sequence and impacted similarly by the chromatin remodeling process. So far, no specific genetic instability is known to arise from the transfer of a human gene into mouse [Deatly et al., ; Tamaoki, ] unless they harbor repetitive elements such as the TNRs characterized in this study. Interestingly, we show that chromatin remodeling results in approximately 20% increase in the frequency of TNR ranging specifically from 145 to 165 repeats.…”

Section: Discussionmentioning

confidence: 99%

Instability of Trinucleotidic Repeats During Chromatin Remodeling in Spermatids

et al. 2014

View full text Add to dashboard Cite

Transient DNA breaks and evidence of DNA damage response have recently been reported during the chromatin remodeling process in haploid spermatids, creating a potential window of enhanced genetic instability. We used flow cytometry to achieve separation of differentiating spermatids into four highly purified populations using transgenic mice harboring 160 CAG repeats within exon 1 of the human Huntington disease gene (HTT). Trinucleotic repeat expansion was found to occur immediately following the chromatin remodeling steps, confirming the genetic instability of the process and pointing to the origin of paternal anticipation observed in some trinucleotidic repeats diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

Instability of Trinucleotidic Repeats During Chromatin Remodeling in Spermatids

et al. 2014

View full text Add to dashboard Cite

show abstract

“…In this report, TGM-PRG-1 and TGM-PRG-3 (Deatly et al, 1998) mice were inoculated in the spinal cord with modified live polioviruses to examine poliovirus neurovirulence and poliomyelitis. This study focuses on the observations of the clinical signs of poliomyelitis in infected mice (similar to those of human disease) which become paralyzed, die, or are unaffected.…”

Section: Introductionmentioning

confidence: 99%

“…By intracranial (IC) inoculation, the two TgPVR mouse lines appear to have similar susceptibilities to wild-type III poliovirus, even though their receptor expression levels differ by threefold (Deatly et al, 1998). The same two mouse lines, TGM-PRG-1 and TGM-PRG-3, were also used in this study, and the results obtained for each mouse line were compared to assess their relative susceptibilities to less neurovirulent type III polioviruses administered IS.…”

Section: Introductionmentioning

confidence: 99%

“…As in the previous study, these two mouse lines were similar in their susceptibility to poliovirus, even when less neurovirulent virus strains were inoculated in the spinal cord. Therefore, the dosage of the PVR gene and the difference in abundance of the receptor in the brain (Deatly et al, 1998) do not affect the overall susceptibility of TgPVR mice to type III polioviruses inoculated in the CNS tissues. However, receptor gene dosage and abundance of pvr in CNS tissues affect the time to onset of disease.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Poliomyelitis in Intraspinally Inoculated Poliovirus Receptor Transgenic Mice

Deatly¹,

Coleman²,

McMullen

et al. 1999

Virology

View full text Add to dashboard Cite

Mice transgenic with the human poliovirus receptor gene develop clinical signs and neuropathology similar to those of human poliomyelitis when neurovirulent polioviruses are inoculated into the central nervous system (CNS). Factors contributing to disease severity and the frequencies of paralysis and mortality include the poliovirus strain, dose, and gender of the mouse inoculated. The more neurovirulent the virus, as defined by monkey challenge results, the higher the rate of paralysis, mortality, and severity of disease. Also, the time to disease onset is shorter for more neurovirulent viruses. Male mice are more susceptible to polioviruses than females. TGM-PRG-3 mice have a 10-fold higher transgene copy number and produce 3-fold more receptor RNA and protein levels in the CNS than TGM-PRG-1 mice. CNS inoculations with type III polioviruses differing in relative neurovirulence show that these mouse lines are similar in disease frequency and severity, demonstrating that differences in receptor gene dosage and concomitant receptor abundance do not affect susceptibility to infection. However, there is a difference in the rate of accumulation of clinical signs. The time to onset of disease is shorter for TGM-PRG-3 than TGM-PRG-1 mice. Thus, receptor dosage affects the rate of appearance of poliomyelitis in these mice.

show abstract

“…Particles produced in this manner can infect cells resistant to the native virus, perhaps suggesting that receptor-induced changes in poliovirus may enable the virus to enter the cell. A recent report indicates that expression of the poliovirus receptor in the mouse gut is insufficient to confer susceptibility to poliovirus following oral inoculation of virus, suggesting that other host factors are essential for viral replication (16). Whether these still undefined host factors represent an entry cofactor or a coreceptor remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

Soluble Receptor-Induced Retroviral Infection of Receptor-Deficient Cells

Damico

Bates

2000

J Virol

View full text Add to dashboard Cite

Current models of retroviral entry hypothesize that interactions between the host cell receptor(s) and viral envelope protein induce structural changes in the envelope protein that convert it to an active conformation, allowing it to mediate fusion with the membrane. Recent evidence supporting this hypothesis is the demonstration that Tva, the receptor for subgroup A avian sarcoma and leukosis virus (ASLV- Retroviral entry is determined by interactions between the host cell receptor and the envelope glycoproteins that spike the surface of the virus. Viral receptors play critical roles in entry and thus are important determinants of both host range and tissue tropism. The entry process is initiated by binding of the viral envelope protein to the receptor on the cell surface, thereby attaching the virus to the host cell. For retroviruses that enter cells at neutral pH such as subgroup A avian sarcoma and leukosis virus (ASLV-A) and the human and simian immunodeficiency viruses (HIV and SIV, respectively), it has been demonstrated that receptor binding triggers structural alterations in the viral glycoprotein. It is postulated that such conformational changes enable the envelope protein to catalyze the fusion of viral and host membranes necessary for delivery of the viral genome into the cell cytoplasm. Thus, retroviral receptors are believed to participate in both attachment of the virus to the cell and regulation of fusogenic properties of the viral envelope proteins.AStudies of both ASLV-A and its receptor, Tva, have provided evidence supporting this model of receptor-triggered activation during retroviral entry. In vitro analysis indicates that soluble receptor binding can induce temperature-dependent changes in the viral envelope protein EnvA (14,30,34). These changes include exposure of the hydrophobic fusion peptide located within the membrane-associated TM subunit of EnvA as well as changes in the receptor-binding SU subunit (30). In addition, binding of purified, soluble receptor converts a soluble form of EnvA into its membrane-binding form (14,34). Conversion to a membrane-binding state appears to involve cooperative interactions within the oligomeric envelope protein that require binding of multiple receptor molecules (14). Similar molecular and biophysical changes have been detected in the pH-dependent envelope protein of influenza virus, hemagglutinin, under low-pH conditions known to convert this protein into one with a fusion-active conformation (19,43). Thus, it has been postulated that Tva binding triggers the conversion of EnvA to a protein in a fusogenic state, which would mediate the membrane fusion-required viral entry.To further substantiate the ability of receptor to activate the fusogenic potential of EnvA and bypass the requirements of a membrane-associated receptor, we evaluated the capacity of soluble Tva (sTva) to trigger ASLV-A infection of receptordeficient cells. Here we report that Tva can act in solution to mediate infection of mammalian cells devoid of endogenous receptor, suggest...

show abstract

Characterization of mouse lines transgenic with the human poliovirus receptor gene

Cited by 13 publications

References 40 publications

Instability of Trinucleotidic Repeats During Chromatin Remodeling in Spermatids

Instability of Trinucleotidic Repeats During Chromatin Remodeling in Spermatids

Poliomyelitis in Intraspinally Inoculated Poliovirus Receptor Transgenic Mice

Soluble Receptor-Induced Retroviral Infection of Receptor-Deficient Cells

Contact Info

Product

Resources

About