Russel S

@article{RN139,

title = {Relative activity of the feline immunodeficiency virus promoter in feline and primate cell lines},

author = {F. Mustafa and P. Jayanth and P. S. Phillip and A. Ghazawi and R. D. Schmidt and K. A. Lew and T. A. Rizvi},

doi = {10.1016/j.micinf.2004.10.015},

issn = {1286-4579 (Print) 1286-4579},

year  = {2005},

date = {2005-01-01},

urldate = {2005-01-01},

journal = {Microbes Infect},

volume = {7},

number = {2},

pages = {233-9},

abstract = {The feline immunodeficiency virus (FIV) long terminal repeat (LTR), compared with some primate lentiviral LTRs, is quite a strong basal promoter. However, it seems to be highly species-specific in function and generally not very efficient in cells of non-feline origin. This study systematically explored the function of the FIV LTR in simian Cos cells compared with its activity in feline and human cells. Our studies, using biologically relevant two- and three-plasmid trans complementation assays followed by semi-quantitative reverse transcriptase PCR, show that the FIV LTR is functional in Cos cells. The results of the Cos experiment are different from previously reported literature and suggest that the strain specificity of the FIV LTR is an important determinant of whether the LTR will be functional in a particular cell type.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN143,

title = {Close proximity of the MPMV CTE to the polyadenylation sequences is important for efficient function in the subgenomic context},

author = {F. Mustafa and P. S. Phillip and P. Jayanth and A. Ghazawi and K. A. Lew and R. D. Schmidt and T. A. Rizvi},

doi = {10.1016/j.virusres.2004.06.014},

issn = {0168-1702 (Print) 0168-1702},

year  = {2004},

date = {2004-01-01},

urldate = {2004-01-01},

journal = {Virus Res},

volume = {105},

number = {2},

pages = {209-18},

abstract = {The constitutive transport element (CTE) of Mason-Pfizer monkey virus (MPMV) is a short cis-acting sequence element critical for virus gene expression. Analogous to the Rev/Rev Responsive Element (RRE) of primate lentiviruses, CTE allows the nucleocytoplasmic transport of unspliced viral mRNAs. In fact, CTE can functionally replace Rev/RRE in the genomic context and has been used successfully in the expression of viral and cellular genes from expression vectors as well. However, unlike RRE, CTE accomplishes this by interacting with cellular factors, making CTE function independent of co-expressed trans factors. Thus, CTE has proven to be a valuable tool in the expression of heterologous genes. Our previous studies have shown that close proximity of CTE to the polyadenylation sequences is important for CTE function in the genomic context. However, it is controversial whether CTE needs to be located spatially close to the polyadenylation sequences in the subgenomic context. Since CTE is being frequently used in expression vectors, we investigated the position dependency of CTE in the heterologous, subgenomic background using both genetic and structural analyses. Our results reveal that similar to the genomic situation, close proximity of CTE to the polyadenylation sequences is important for its function in the heterologous subgenomic context.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN140,

title = {Mutational analysis of the predicted secondary RNA structure of the Mason-Pfizer monkey virus packaging signal},

author = {F. Mustafa and K. A. Lew and R. D. Schmidt and M. T. Browning and T. A. Rizvi},

doi = {10.1016/j.virusres.2003.09.012},

issn = {0168-1702 (Print) 0168-1702},

year  = {2004},

date = {2004-01-01},

urldate = {2004-01-01},

journal = {Virus Res},

volume = {99},

number = {1},

pages = {35-46},

abstract = {The 5' end of the Mason-Pfizer monkey virus (MPMV) genomic RNA has been predicted to fold into a complex stem/loop structure that is thought to play a role in specific RNA encapsidation. In this study, we used a set of mutations that either abrogated or recreated the first four stem loops predicted within the 5' untranslated region (5' UTR) for effects on RNA packaging. Test of these mutations in our biological assay revealed that only stem loop 1 (SL1) was important for the packaging potential of MPMV, while mutations in none of the other stem loops affected packaging significantly. Interestingly, it was the primary sequence of SL1 RNA and not its secondary structure that affected packaging since compensatory mutations that reformed SL1 were unable to restore the packaging efficiency of the retroviral vector. Additionally, our mutational analysis reveals that stem loop 4, predicted to be the major packaging determinant of MPMV, does not seem to have a significant role in packaging. Finally, results of the biological effects of the structural mutations are discussed in relation to their effects on the folding potential of the various stem loops.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN141,

title = {Delineation of sequences important for efficient packaging of feline immunodeficiency virus RNA},

author = {M. T. Browning and F. Mustafa and R. D. Schmidt and K. A. Lew and T. A. Rizvi},

doi = {10.1099/vir.0.18886-0},

issn = {0022-1317 (Print) 0022-1317},

year  = {2003},

date = {2003-01-01},

urldate = {2003-01-01},

journal = {J Gen Virol},

volume = {84},

number = {Pt 3},

pages = {621-627},

abstract = {We have used systematic deletion analysis of the 5' untranslated region (UTR) of the feline immunodeficiency virus (FIV) genome, both in the presence and absence of various amounts of gag, to define the cis-acting sequences responsible for efficient RNA packaging. Our analyses revealed that the primary FIV packaging signal consists of two essential core elements located within the first 90-120 bp of the 5'UTR and the first 90 bp of the gag gene. Interestingly, the region between the major splice donor (SD) and gag, including approximately 130-160 bp upstream of the SD, is dispensable for encapsidation. Finally, other determinants of packaging were found to be present in the viral LTR and/or within the 3' end of the viral genome. Taken together, our results suggest that the primary packaging determinants of FIV are multipartite and discontinuous, composed of two elements within the 5'UTR and gag gene.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN145,

title = {Sequences within the gag gene of feline immunodeficiency virus (FIV) are important for efficient RNA encapsidation},

author = {M. T. Browning and F. Mustafa and R. D. Schmidt and K. A. Lew and T. A. Rizvi},

doi = {10.1016/s0168-1702(03)00098-4},

issn = {0168-1702 (Print) 0168-1702},

year  = {2003},

date = {2003-01-01},

urldate = {2003-01-01},

journal = {Virus Res},

volume = {93},

number = {2},

pages = {199-209},

abstract = {Feline immunodeficiency virus (FIV)-based retroviral vector systems are being developed for human gene therapy. Consequently, it has become important to know the precise sequence requirements for the packaging of FIV genome so that such sequences can be eliminated from transfer vectors post-transduction for improved safety. Recently, we have shown that sequences both within the 5'-untranslated leader region (UTR) and the 5'-end of gag are required for efficient packaging and transduction of FIV-based vectors. However, the extent of gag sequence important in the encapsidation process is not clear as well as their relative contribution to packaging. In this study, using a biologically relevant packaging system, we demonstrate that at the most 100 bp of gag sequences are sufficient for efficient RNA packaging in conjunction with the 5'-UTR and no other sequences within the next 600 bp of gag exist that affect packaging. In addition, we show that sequences within gag do not simply act as spatial elements to stabilize other structural determinants of packaging located within the 5'-UTR, but are important in themselves for the encapsidation process.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN131,

title = {Sequences within both the 5' untranslated region and the gag gene are important for efficient encapsidation of Mason-Pfizer monkey virus RNA},

author = {R. D. Schmidt and F. Mustafa and K. A. Lew and M. T. Browning and T. A. Rizvi},

doi = {10.1016/s0042-6822(02)00101-0},

issn = {0042-6822 (Print) 0042-6822},

year  = {2003},

date = {2003-01-01},

urldate = {2003-01-01},

journal = {Virology},

volume = {309},

number = {1},

pages = {166-78},

abstract = {It has previously been shown that the 5' untranslated leader region (UTR), including about 495 bp of the gag gene, is sufficient for the efficient encapsidation and propagation of Mason-Pfizer monkey virus (MPMV) based retroviral vectors. In addition, a deletion upstream of the major splice donor, SD, has been shown to adversely affect MPMV RNA packaging. However, the precise sequence requirement for the encapsidation of MPMV genomic RNA within the 5' UTR and gag remains largely unknown. In this study, we have used a systematic deletion analysis of the 5' UTR and gag gene to define the cis-acting sequences responsible for efficient MPMV RNA packaging. Using an in vivo packaging and transduction assay, our results reveal that the MPMV packaging signal is primarily found within the first 30 bp immediately downstream of the primer binding site. However, its function is dependent upon the presence of the last 23 bp of the 5' UTR and approximately the first 100 bp of the gag gene. Thus, sequences that affect MPMV RNA packaging seem to reside both upstream and downstream of the major splice donor with the downstream region responsible for the efficient functioning of the upstream primary packaging determinant.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN147,

title = {Postnatal pre- and postexposure passive immunization strategies: protection of neonatal macaques against oral simian-human immunodeficiency virus challenge},

author = {R. Hofmann-Lehmann and J. Vlasak and R. A. Rasmussen and S. Jiang and P. L. Li and T. W. Baba and D. C. Montefiori and B. J. Bernacky and T. A. Rizvi and R. Schmidt and L. R. Hill and M. E. Keeling and H. Katinger and G. Stiegler and L. A. Cavacini and M. R. Posner and R. M. Ruprecht},

doi = {10.1034/j.1600-0684.2002.01014.x},

issn = {0047-2565 (Print) 0047-2565},

year  = {2002},

date = {2002-01-01},

urldate = {2002-01-01},

journal = {J Med Primatol},

volume = {31},

number = {3},

pages = {109-19},

abstract = {Simian-human immunodeficiency viruses (SHIV) allow the evaluation of antiviral strategies that target the envelope glycoproteins of the human immunodeficiency virus 1 (HIV-1) in macaques. We previously protected neonates from oral challenge with cell-free SHIV-vpu+ by passive immunization with synergistic human neutralizing monoclonal antibodies (mAbs) (Baba et al., Nat Med 6:200-206, 2000). mAbs were administered prenatally to pregnant dams and postnatally to the neonates. Here, we used solely postnatal or postexposure mAb treatment, thus significantly reducing the amount of mAbs necessary. All neonatal monkeys were also protected with these abbreviated mAb regimens. Our results are directly relevant for humans because we used mAbs that target HIV-1 envelope glycoproteins. Thus, the large-scale use of passive immunization with neutralizing mAbs may be feasible in human neonates. The mAbs, being natural human proteins, can be expected to have low toxicity. Passive immunization has promise to prevent intrapartum as well as milk-borne virus transmission from HIV-1-infected women to their infants.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN78,

title = {Passive immunization against oral AIDS virus transmission: an approach to prevent mother-to-infant HIV-1 transmission?},

author = {R. Hofmann-Lehmann and R. A. Rasmussen and J. Vlasak and B. A. Smith and T. W. Baba and V. Liska and D. C. Montefiori and H. M. McClure and D. C. Anderson and B. J. Bernacky and T. A. Rizvi and R. Schmidt and L. R. Hill and M. E. Keeling and H. Katinger and G. Stiegler and M. R. Posner and L. A. Cavacini and T. C. Chou and R. M. Ruprecht},

doi = {10.1034/j.1600-0684.2001.d01-52.x},

issn = {0047-2565 (Print) 0047-2565},

year  = {2001},

date = {2001-01-01},

urldate = {2001-01-01},

journal = {J Med Primatol},

volume = {30},

number = {4},

pages = {190-6},

abstract = {To develop immunoprophylaxis regimens against mother-to-child human immunodeficiency virus type 1 (HIV-1) transmission, we established a simian-human immunodeficiency virus (SHIV) model in neonatal macaques that mimics intrapartum mucosal virus exposure (T.W. Baba, J. Koch, E.S. Mittler et al: AIDS Res Hum Retroviruses 10:351-357, 1994). We protected four neonates from oral SHIV-vpu+ challenge by ante- and postpartum treatment with a synergistic triple combination of immunoglobulin (Ig) G1 human anti-HIV-1 neutralizing monoclonal antibodies (mAbs) (T.W. Baba, V. Liska, R. Hofmann-Lehmann et al: Nature Med 6:200-206, 2000), which recognize the CD4-binding site of Env, a glycosylation-dependent gp120, or a linear gp41 epitope. Two neonates that received only postpartum mAbs were also protected from oral SHIV-vpu+ challenge, indicating that postpartum treatment alone is sufficient. Next, we evaluated a similar mAb combination against SHIV89.6P, which encodes env of primary HIV89.6. One of four mAb-treated neonates was protected from infection and two maintained normal CD4+ T-cell counts. We conclude that the epitopes recognized by the three mAbs are important determinants for achieving protection. Combination immunoprophylaxis with synergistic mAbs seems promising to prevent maternal HIV-1 transmission in humans.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN96,

title = {Postnatal passive immunization of neonatal macaques with a triple combination of human monoclonal antibodies against oral simian-human immunodeficiency virus challenge},

author = {R. Hofmann-Lehmann and J. Vlasak and R. A. Rasmussen and B. A. Smith and T. W. Baba and V. Liska and F. Ferrantelli and D. C. Montefiori and H. M. McClure and D. C. Anderson and B. J. Bernacky and T. A. Rizvi and R. Schmidt and L. R. Hill and M. E. Keeling and H. Katinger and G. Stiegler and L. A. Cavacini and M. R. Posner and T. C. Chou and J. Andersen and R. M. Ruprecht},

doi = {10.1128/jvi.75.16.7470-7480.2001},

issn = {0022-538X (Print) 0022-538x},

year  = {2001},

date = {2001-01-01},

urldate = {2001-01-01},

journal = {J Virol},

volume = {75},

number = {16},

pages = {7470-80},

abstract = {To develop prophylaxis against mother-to-child human immunodeficiency virus (HIV) transmission, we established a simian-human immunodeficiency virus (SHIV) infection model in neonatal macaques that mimics intrapartum mucosal virus exposure (T. W. Baba et al., AIDS Res. Hum. Retroviruses 10:351-357, 1994). Using this model, neonates were protected from mucosal SHIV-vpu(+) challenge by pre- and postnatal treatment with a combination of three human neutralizing monoclonal antibodies (MAbs), F105, 2G12, and 2F5 (Baba et al., Nat. Med. 6:200-206, 2000). In the present study, we used this MAb combination only postnatally, thereby significantly reducing the quantity of antibodies necessary and rendering their potential use in humans more practical. We protected two neonates with this regimen against oral SHIV-vpu(+) challenge, while four untreated control animals became persistently infected. Thus, synergistic MAbs protect when used as immunoprophylaxis without the prenatal dose. We then determined in vitro the optimal MAb combination against the more pathogenic SHIV89.6P, a chimeric virus encoding env of the primary HIV89.6. Remarkably, the most potent combination included IgG1b12, which alone does not neutralize SHIV89.6P. We administered the combination of MAbs IgG1b12, 2F5, and 2G12 postnatally to four neonates. One of the four infants remained uninfected after oral challenge with SHIV89.6P, and two infants had no or a delayed CD4(+) T-cell decline. In contrast, all control animals had dramatic drops in their CD4(+) T cells by 2 weeks postexposure. We conclude that our triple MAb combination partially protected against mucosal challenge with the highly pathogenic SHIV89.6P. Thus, combination immunoprophylaxis with passively administered synergistic human MAbs may play a role in the clinical prevention of mother-to-infant transmission of HIV type 1.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN16,

title = {Protection of neonatal macaques against experimental SHIV infection by human neutralizing monoclonal antibodies},

author = {R. M. Ruprecht and R. Hofmann-Lehmann and B. A. Smith-Franklin and R. A. Rasmussen and V. Liska and J. Vlasak and W. Xu and T. W. Baba and A. L. Chenine and L. A. Cavacini and M. R. Posner and H. Katinger and G. Stiegler and B. J. Bernacky and T. A. Rizvi and R. Schmidt and L. R. Hill and M. E. Keeling and D. C. Montefiori and H. M. McClure},

doi = {10.1016/s1246-7820(01)00187-2},

issn = {1246-7820 (Print) 1246-7820},

year  = {2001},

date = {2001-01-01},

urldate = {2001-01-01},

journal = {Transfus Clin Biol},

volume = {8},

number = {4},

pages = {350-8},

abstract = {Neonatal macaques were completely protected against oral challenge with SHIV-vpu+, a simian-human immunodeficiency virus that encodes the envelope gene of a laboratory-adapted HIV strain, by pre- and post-natal treatment with a triple combination of human neutralizing monoclonal antibodies (mAbs). The mAbs were directed either against the CD4 binding site, a glycosylation-dependent gp120 epitope, or against a linear epitope on gp41. This triple combination was highly synergistic in vitro and neutralized primary HIV completely. Subsequently, oral challenge was performed with pathogenic SHIV89.6P, an animal-passaged variant of a chimeric virus that encodes the envelope gene of the primary, dual-tropic HIV89.6. Only post-natal treatment with a similar triple mAb combination was used. One out of 4 mAb-treated infants was completely protected from infection. In the other 3 treated animals, there was a tendency towards lower peak viral RNA loads compared with untreated controls. Two out of 4 mAb-treated infants maintained normal CD4+ T-cell numbers, in contrast to all controls that had steep declines at 2 weeks post-challenge. We conclude that the triple mAb combination significantly protected the neonates, even against mucosal challenge with pathogenic SHIV89.6P. Passively administered synergistic human mAbs may play a role in preventing mother-infant transmission of HIV, both against intrapartum transmission as well as against infection through breast milk. As passive immunization is a tool to assess correlates of immune protection, we conclude that the epitopes recognized by the mAbs in our combinations are important for AIDS vaccine development. Future passive immunization studies may reveal other important conserved epitopes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN114,

title = {Primate and feline lentivirus vector RNA packaging and propagation by heterologous lentivirus virions},

author = {M. T. Browning and R. D. Schmidt and K. A. Lew and T. A. Rizvi},

doi = {10.1128/jvi.75.11.5129-5140.2001},

issn = {0022-538X (Print) 0022-538x},

year  = {2001},

date = {2001-01-01},

urldate = {2001-01-01},

journal = {J Virol},

volume = {75},

number = {11},

pages = {5129-40},

abstract = {Development of safe and effective gene transfer systems is critical to the success of gene therapy protocols for human diseases. Currently, several primate lentivirus-based gene transfer systems, such as those based on human and simian immunodeficiency viruses (HIV/SIV), are being tested; however, their use in humans raises safety concerns, such as the generation of replication-competent viruses through recombination with related endogenous retroviruses or retrovirus-like elements. Due to the greater phylogenetic distance from primate lentiviruses, feline immunodeficiency virus (FIV) is becoming the lentivirus of choice for human gene transfer systems. However, the safety of FIV-based vector systems has not been tested experimentally. Since lentiviruses such as HIV-1 and SIV have been shown to cross-package their RNA genomes, we tested the ability of FIV RNA to get cross-packaged into primate lentivirus particles such as HIV-1 and SIV, as well as a nonlentiviral retrovirus such as Mason-Pfizer monkey virus (MPMV), and vice versa. Our results reveal that FIV RNA can be cross-packaged by primate lentivirus particles such as HIV-1 and SIV and vice versa; however, a nonlentivirus particle such as MPMV is unable to package FIV RNA. Interestingly, FIV particles can package MPMV RNA but cannot propagate the vector RNA further for other steps of the retrovirus life cycle. These findings reveal that diverse retroviruses are functionally more similar than originally thought and suggest that upon coinfection of the same host, cross- or copackaging may allow distinct retroviruses to generate chimeric variants with unknown pathogenic potential.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN112,

title = {Human neutralizing monoclonal antibodies of the IgG1 subtype protect against mucosal simian-human immunodeficiency virus infection},

author = {T. W. Baba and V. Liska and R. Hofmann-Lehmann and J. Vlasak and W. Xu and S. Ayehunie and L. A. Cavacini and M. R. Posner and H. Katinger and G. Stiegler and B. J. Bernacky and T. A. Rizvi and R. Schmidt and L. R. Hill and M. E. Keeling and Y. Lu and J. E. Wright and T. C. Chou and R. M. Ruprecht},

doi = {10.1038/72309},

issn = {1078-8956 (Print) 1078-8956},

year  = {2000},

date = {2000-01-01},

urldate = {2000-01-01},

journal = {Nat Med},

volume = {6},

number = {2},

pages = {200-6},

abstract = {Although maternal human immunodeficiency virus type 1 (HIV-1) transmission occurs during gestation, intrapartum and postpartum (by breast-feeding), 50-70% of all infected children seem to acquire HIV-1 shortly before or during delivery. Epidemiological evidence indicates that mucosal exposure is an important aspect of intrapartum HIV transmission. A simian immunodeficiency virus (SIV) macaque model has been developed that mimics the mucosal exposure that can occur during intrapartum HIV-1 transmission. To develop immunoprophylaxis against intrapartum HIV-1 transmission, we used SHIV-vpu+ (refs. 5,6), a chimeric simian-human virus that encodes the env gene of HIV-IIIB. Several combinations of human monoclonal antibodies against HIV-1 have been identified that neutralize SHIV-vpu+ completely in vitro through synergistic interaction. Here, we treated four pregnant macaques with a triple combination of the human IgG1 monoclonal antibodies F105, 2G12 and 2F5. All four macaques were protected against intravenous SHIV-vpu+ challenge after delivery. The infants received monoclonal antibodies after birth and were challenged orally with SHIV-vpu+ shortly thereafter. We found no evidence of infection in any infant during 6 months of follow-up. This demonstrates that IgG1 monoclonal antibodies protect against mucosal lentivirus challenge in neonates. We conclude that epitopes recognized by the three monoclonal antibodies are important determinants for achieving substantial protection, thus providing a rational basis for AIDS vaccine development.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN27,

title = {Mason-Pfizer monkey virus (MPMV) constitutive transport element (CTE) functions in a position-dependent manner},

author = {T. A. Rizvi and R. D. Schmidt and K. A. Lew},

doi = {10.1006/viro.1997.8728},

issn = {0042-6822 (Print) 0042-6822},

year  = {1997},

date = {1997-01-01},

urldate = {1997-01-01},

journal = {Virology},

volume = {236},

number = {1},

pages = {118-29},

abstract = {The Mason-Pfizer monkey virus (MPMV) constitutive transport element (CTE) is a cis-acting RNA element located in the 3' untranslated region (UTR) of the viral genome. The HIV-1 and SIV Rev/RRE regulatory system can be replaced with MPMV CTE (Bray et al., 1994; Zolotukhin et al., 1994; Rizvi et al., 1996a); similarly, CTE function can also be replaced by the HIV or SIV Rev/RRE regulatory system (Rizvi et al., 1996b; Ernst et al., 1997). In addition, we have shown that in the context of the SIV genome, position is important for CTE function (Rizvi et al., 1996a). To determine the importance of position for CTE function in the context of the MPMV genome, MPMV molecular clones were generated by deleting CTE or removing it from the 3' UTR and placing it in the approximately 40 bp of intervening sequences between the pol termination codon and env initiation codon. A test of these molecular clones in a single round of replication assay revealed that deletion or displacement of CTE in the intervening sequences between pol and env completely abrogated virus replication. Western blot analysis of cell lysates and pelleted culture supernatants revealed negligible amounts of Pr78 Gag/Pol precursor and the processed p27(gag) when CTE was deleted or displaced. Slot blot analysis of fractionated RNAs revealed entrapment of the viral Gag/Pol mRNA in the nucleus with CTE deletion or displacement. Upon reinsertion of CTE in the original genomic position of clones with the deleted or displaced CTE, virus replication, Gag/Pol protein production, and nucleocytoplasmic transport of viral mRNA were restored to normal levels. Displacement of CTE to the 5' UTR immediately upstream of the Gag initiation codon also resulted in aberrant Gag/Pol protein production and nucleocytoplasmic transport of viral RNA. Reinsertion of CTE at the original genomic position of the clone with CTE displacement at the 5' UTR restored normal Gag/Pol protein production and RNA transport, demonstrating that the 3' terminal position of CTE is important for its function. To explore why the 3' terminal location of CTE is important, heterologous DNA sequences of increasing lengths were inserted between CTE and the polyadenylation (poly(A)) signal of the virus to augment the distance between the two cis-acting elements. Test of these constructs revealed that CTE function was progressively lost with incremental increase in distance between CTE and poly(A). To explore this relationship further, CTE was displaced to the env region approximately 2000 bp upstream of the poly(A) signal which abrogated CTE function. However, cloning of poly(A) signal to approximately 200 bp downstream of CTE in the env region (the natural distance between CTE and poly(A)) restored CTE function. Together, these results demonstrate that the close proximity of CTE to the poly(A) signal is important for CTE function, suggesting a functional interaction between CTE and the polyadenylation machinery.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN146,

title = {Rhesus thymic/liver xenografts in severe combined immunodeficient mice: immunologic reconstitution and intrathymic infection with simian immunodeficiency virus},

author = {A. A. Binhazim and T. A. Rizvi and L. G. Coghlan and K. Lew and R. Schmidt and P. K. Wong},

url = {https://pubmed.ncbi.nlm.nih.gov/8804357/},

issn = {0023-6837 (Print) 0023-6837},

year  = {1996},

date = {1996-01-01},

urldate = {1996-01-01},

journal = {Lab Invest},

volume = {75},

number = {3},

pages = {339-48},

abstract = {By serving as host recipients of xenografts from both humans and animals, severe combined immunodeficient (SCID) mice have become valuable to many laboratories interested in examining the pathophysiology of different diseases. To gain insight into the usefulness of the SCID mutation in retrovirus research, rhesus monkey fetal hematolymphoid tissues (liver and thymus) were used to construct a SCID-rhesus chimeric mouse (SCID-rh) and were engrafted in the renal capsule. The size and maturation of the thymic engrafts were monitored grossly, histologically, and immunologically. SCID mice were tolerant to rhesus tissues, and thymic engrafts contained thymocytes at different stages of maturation and differentiation that had morphologic features similar to age-matched rhesus thymus. Mature single positive CD2+, CD4+, and CD8+ T lymphocytes that were phenotypically similar to rhesus T lymphocytes were present at low levels (2% to 5%) in the peripheral blood and at moderately higher levels (7% to 15%) in the spleens of SCID-rh mice obtained between 12 and 15 weeks after thymus/liver engraftment. Within 3 weeks after engraftment, > 85% of the thymocytes in the thymic engrafts were immature double positive CD4+CD8+ T cells. The highest number of positive cells were seen in thymic engrafts obtained at 12 to 18 weeks. During these weeks, > 90% of the cells were double positive (CD2+CD4+, CD2+CD8+, and CD4+CD8+). After infection of the engrafted thymus tissue with simian immonodeficiency virus (SIVmac239), PCR analysis revealed successful viral infection of engrafts at 2 and 4 weeks after infection. No significant histopathologic and flow cytometric changes were observed in the thymic engrafts at 2 and 4 weeks after infection. An unrelated lesion of thymic lymphomas involving the SCID host thymus was seen in 12% of the mice. The data presented herein suggest that the SCID-rh is a valuable model for specific studies related to thymus-retrovirus interaction and that it could be used for further studies. The results are discussed in relation to current knowledge of thymus involvement during simian and human immunodeficiency virus infection.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN93,

title = {Role of Mason-Pfizer monkey virus (MPMV) constitutive transport element (CTE) in the propagation of MPMV vectors by genetic complementation using homologous/heterologous env genes},

author = {T. A. Rizvi and K. A. Lew and Jr. E. C. Murphy and R. D. Schmidt},

doi = {10.1006/viro.1996.0558},

issn = {0042-6822 (Print) 0042-6822},

year  = {1996},

date = {1996-01-01},

urldate = {1996-01-01},

journal = {Virology},

volume = {224},

number = {2},

pages = {517-32},

abstract = {To study Mason-Pfizer monkey virus (MPMV) replication over a single round, virus particles were generated that contain a replication-defective vector encoding a dominant selectable marker, the hygromycin B phosphotransferase (hyg) gene. Genetic complementation with a homologous MPMV envelope glycoprotein (Env-gp) or pseudotyping by several heterologous Env-gps from a variety of viruses resulted in infectious MPMV particles containing the replication-defective RNA. Recently, it has been shown that human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) Rev and Rev-responsive element (RRE) functions can be substituted in vitro by a cis-acting sequence, the constitutive transport element (CTE), from simian type D retroviruses like MPMV and simian retrovirus type 1 (SRV-1). To determine whether CTE of MPMV is necessary for MPMV nucleic acid propagation, an MPMV vector that lacked the terminally located CTE was generated. Propagation of this vector was completely abrogated in the absence of CTE, showing the importance of CTE in MPMV replication. Insertion of CTE back into the MPMV genome in the sense orientation rescued replication to wild-type levels. Slot-blot analysis of nuclear versus cytoplasmic RNA fractions revealed that most of the messages were sequestered in the nucleus of cells transfected with the CTE(-) vectors and very little was transported to the cytoplasm. To test whether HIV-1 or SIV RREs could complement CTE function, the HIV-1 or SIV RREs were inserted in the CTE(-) vectors, trans complementation of CTE(-)RRE(+) vectors with Env-and Rev-expression plasmids rescued propagation of the CTE(-) vectors. Computer analysis predicted an RNA secondary structure in MPMV CTE analogous to the HIV-1 and SIV RREs that could form three stable stem loops, the first of which contains a site similar to the Rev-binding domain in the HIV-1 RRE. The presence of a higher-order CTE structure was analyzed by mutational analysis. We conclude that CTE is important in the replication of MPMV and affects the nucleocytoplasmic transport and/or stability of viral messages similar to the Rev/RRE regulatory system of HIV-1 and SIV.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN86,

title = {Rev/RRE-independent Mason-Pfizer monkey virus constitutive transport element-dependent propagation of SIVmac239 vectors using a single round of replication assay},

author = {T. A. Rizvi and R. D. Schmidt and K. A. Lew and M. E. Keeling},

doi = {10.1006/viro.1996.0444},

issn = {0042-6822 (Print) 0042-6822},

year  = {1996},

date = {1996-01-01},

urldate = {1996-01-01},

journal = {Virology},

volume = {222},

number = {2},

pages = {457-63},

abstract = {In a step toward creating live-attenuated or DNA subunit vaccines for AIDS, the replication of simian immunodeficiency virus (SIV) was studied independently of the Rev and RRE (Rev-responsive element) regulatory system, over a single round. To accomplish this, the env gene of an SIV vector was made defective by the insertion of a SV40 promoter/enhancer hygromycin B phosphotransferase gene cassette. Using this vector as the backbone, molecular clones of SIV were generated that contained a mutated Rev, Rev(-), a deleted RRE, RRE(-), or both, Rev(-)RRE(-). It has been shown recently that human immunodeficiency virus type 1 (HIV-1) Rev and RRE functions can be replaced in vitro by a cis-acting sequence, constitutive transport element (CTE), from simian type D retroviruses. To determine whether such a cis-acting element from Mason-Pfizer monkey virus (MPMV) would substitute for SIV Rev and RRE functions, the MPMV CTE was inserted either into the Nef ORF or at the junction of vpx and vpr of our Rev(-), RRE(-), and Rev(-)RRE(-) SIV molecular clones. Cell-free viral stocks harvested from Cos cells following transfections of these molecular clones revealed that these stocks were infectious over a single round of replication; however, their replication was attenuated 16-fold compared to that of wild-type virus. In addition, our experiments revealed that CTE functions in a position-dependent manner such that its insertion at the junction of vpx and vpr attenuated SIV replication 8- to 12-fold compared to the attenuation observed when it was inserted in the nef region. Our results demonstrate that MPMV CTE is capable of substituting for SIV Rev and RRE functions, resulting in an attenuated ability to produce infectious virus.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}