Functional Characterization of the Protease of Human Endogenous Retrovirus, K10:  Can It Complement HIV-1 Protease?†

Biochemistry ◽  
1998 ◽  
Vol 37 (49) ◽  
pp. 17137-17144 ◽  
Author(s):  
Eric M. Towler ◽  
Sergei V. Gulnik ◽  
T. N. Bhat ◽  
Dong Xie ◽  
Elena Gustschina ◽  
...  
Keyword(s):  
Functional Characterization ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Hiv 1

scholarly journals Molecular cloning and functional characterization of the human endogenous retrovirus K113

Virology ◽  
2008 ◽  
Vol 371 (1) ◽  
pp. 216-225 ◽  
Author(s):  
Nadine Beimforde ◽  
Kirsten Hanke ◽  
Ismahen Ammar ◽  
Reinhard Kurth ◽  
Norbert Bannert
Keyword(s):  
Molecular Cloning ◽  
Functional Characterization ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus

scholarly journals Human Endogenous Retrovirus Expression Is Inversely Associated with Chronic Immune Activation in HIV-1 Infection

PLoS ONE ◽  
2012 ◽  
Vol 7 (8) ◽  
pp. e41021 ◽  
Author(s):  
Christopher E. Ormsby ◽  
Devi SenGupta ◽  
Ravi Tandon ◽  
Steven G. Deeks ◽  
Jeffrey N. Martin ◽  
...  
Keyword(s):  
Immune Activation ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Chronic Immune Activation ◽  
Hiv 1

scholarly journals Membrane Binding and Subcellular Localization of Retroviral Gag Proteins Are Differentially Regulated by MA Interactions with Phosphatidylinositol-(4,5)-Bisphosphate and RNA

mBio ◽  
2014 ◽  
Vol 5 (6) ◽  
Author(s):  
Jingga Inlora ◽  
David R. Collins ◽  
Marc E. Trubin ◽  
Ji Yeon J. Chung ◽  
Akira Ono
Keyword(s):  
Virus Assembly ◽  
Membrane Binding ◽  
Endogenous Retrovirus ◽  
Single Amino Acid ◽  
Human Endogenous Retrovirus ◽  
Structural Protein ◽  
Acidic Phospholipid ◽  
Specific Localization ◽  
Hiv 1

ABSTRACTThe matrix (MA) domain of HIV-1 mediates proper Gag localization and membrane binding via interaction with a plasma-membrane (PM)-specific acidic phospholipid, phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P2]. HIV-1 MA also interacts with RNA, which prevents Gag from binding to membranes containing phosphatidylserine, a prevalent cellular acidic phospholipid. These results suggest that the MA-bound RNA promotes PM-specific localization of HIV-1 Gag by blocking nonspecific interactions with cellular membranes that do not contain PI(4,5)P2. To examine whether PI(4,5)P2dependence and RNA-mediated inhibition collectively determine MA phenotypes across a broad range of retroviruses and elucidate the significance of their interrelationships, we compared a panel of Gag-leucine zipper constructs (GagLZ) containing MA of different retroviruses. We found thatin vitromembrane binding of GagLZ via HIV-1 MA and Rous sarcoma virus (RSV) MA is both PI(4,5)P2dependent and susceptible to RNA-mediated inhibition. The PM-specific localization and virus-like particle (VLP) release of these GagLZ proteins are severely impaired by overexpression of a PI(4,5)P2-depleting enzyme, polyphosphoinositide 5-phosphatase IV (5ptaseIV). In contrast, membrane binding of GagLZ constructs that contain human T-lymphotropic virus type 1 (HTLV-1) MA, murine leukemia virus (MLV) MA, and human endogenous retrovirus K (HERV-K) MA is PI(4,5)P2independent and not blocked by RNA. The PM localization and VLP release of these GagLZ chimeras were much less sensitive to 5ptaseIV expression. Notably, single amino acid substitutions that confer a large basic patch rendered HTLV-1 MA susceptible to the RNA-mediated block, suggesting that RNA readily blocks MA containing a large basic patch, such as HIV-1 and RSV MA. Further analyses of these MA mutants suggest a possibility that HIV-1 and RSV MA acquired PI(4,5)P2dependence to alleviate the membrane binding block imposed by RNA.IMPORTANCEMA basic residues in the HIV-1 structural protein Gag interact with phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P2] and RNA. RNA inhibits HIV-1 MA binding to non-PI(4,5)P2acidic lipids. This inhibition may promote PM specificity of Gag membrane binding, an early essential step in virus assembly. However, whether and how relationships between these interactions have developed among retroviruses are poorly understood. In this study, by comparing diverse retroviral MA domains, we elucidated a strong correlation among PI(4,5)P2dependence, susceptibility to RNA-mediated inhibition, and cellular behaviors of Gag. Mutagenesis analyses suggest that a large basic patch on MA is sufficient to confer susceptibility to RNA-mediated inhibition but not for PI(4,5)P2-dependent membrane binding. Our findings highlight RNA’s role as a general blocker of large basic patches and suggest a possibility that some retroviruses, including HIV-1, have evolved to bind PI(4,5)P2, while others have adopted smaller basic patches on their MA domains, to overcome the RNA-mediated restriction of membrane binding.

scholarly journals HIV-1 Interacts with Human Endogenous Retrovirus K (HML-2) Envelopes Derived from Human Primary Lymphocytes

2014 ◽  
Vol 88 (11) ◽  
pp. 6213-6223 ◽  
Author(s):  
D. Brinzevich ◽  
G. R. Young ◽  
R. Sebra ◽  
J. Ayllon ◽  
S. M. Maio ◽  
...  
Keyword(s):  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Hiv 1

scholarly journals Characterization of Human Endogenous Retrovirus Type K Virus-like Particles Generated from Recombinant Baculoviruses

Virology ◽  
1997 ◽  
Vol 233 (2) ◽  
pp. 280-291 ◽  
Author(s):  
Ralf R. Tönjes ◽  
Klaus Boller ◽  
Christiane Limbach ◽  
Raimond Lugert ◽  
Reinhard Kurth
Keyword(s):  
Endogenous Retrovirus ◽  
Recombinant Baculoviruses ◽  
Human Endogenous Retrovirus ◽  
Virus Like Particles ◽  
Type K

scholarly journals Functional Characterization of Two scFv-Fc Antibodies from an HIV Controller Selected on Soluble HIV-1 Env Complexes: A Neutralizing V3- and a Trimer-Specific gp41 Antibody

PLoS ONE ◽  
2014 ◽  
Vol 9 (5) ◽  
pp. e97478 ◽  
Author(s):  
Maria Trott ◽  
Svenja Weiß ◽  
Sascha Antoni ◽  
Joachim Koch ◽  
Hagen von Briesen ◽  
...  
Keyword(s):  
Functional Characterization ◽  
Hiv 1

scholarly journals Mutational Definition of Functional Domains within the Rev Homolog Encoded by Human Endogenous Retrovirus K

2000 ◽  
Vol 74 (20) ◽  
pp. 9353-9361 ◽  
Author(s):  
Hal P. Bogerd ◽  
Heather L. Wiegand ◽  
Jin Yang ◽  
Bryan R. Cullen
Keyword(s):  
Nuclear Export ◽  
Biological Activities ◽  
Endogenous Retrovirus ◽  
Viral Rna ◽  
Human Endogenous Retrovirus ◽  
Nuclear Rna ◽  
Rna Export ◽  
Nuclear Rna Export ◽  
Hiv 1 ◽  
Rev Protein

ABSTRACT Nuclear export of the incompletely spliced mRNAs encoded by several complex retroviruses, including human immunodeficiency virus type 1 (HIV-1), is dependent on a virally encoded adapter protein, termed Rev in HIV-1, that directly binds both to a cis-acting viral RNA target site and to the cellular Crm1 export factor. Human endogenous retrovirus K, a family of ancient endogenous retroviruses that is not related to the exogenous retrovirus HIV-1, was recently shown to also encode a Crm1-dependent nuclear RNA export factor, termed K-Rev. Although HIV-1 Rev and K-Rev display little sequence identity, they share the ability not only to bind to Crm1 and to RNA but also to form homomultimers and shuttle between nucleus and cytoplasm. We have used mutational analysis to identify sequences in the 105-amino-acid K-Rev protein required for each of these distinct biological activities. While mutations in K-Rev that inactivate any one of these properties also blocked K-Rev-dependent nuclear RNA export, several K-Rev mutants were comparable to wild type when assayed for any of these individual activities yet nevertheless defective for RNA export. Although several nonfunctional K-Rev mutants acted as dominant negative inhibitors of K-Rev-, but not HIV-1 Rev-, dependent RNA export, these were not defined by their inability to bind to Crm1, as is seen with HIV-1 Rev. In total, this analysis suggests a functional architecture for K-Rev that is similar to, but distinct from, that described for HIV-1 Rev and raises the possibility that viral RNA export mediated by the ∼25 million-year-old K-Rev protein may require an additional cellular cofactor that is not required for HIV-1 Rev function.

Genetic and Functional Characterization of the LTR of HIV-1 Subtypes A and C Circulating in India

2007 ◽  
Vol 23 (11) ◽  
pp. 1428-1433 ◽  
Author(s):  
Milka A. Rodriguez ◽  
Chengli Shen ◽  
Deena Ratner ◽  
Ramesh S. Paranjape ◽  
Smita S. Kulkarni ◽  
...  
Keyword(s):  
Functional Characterization ◽  
Hiv 1
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