Analysis of Human Immunodeficiency Virus Type 1 Containing HERV-K Protease

Padow, Marcus; Lai, Lilin; Fisher, Robert J.; Zhou, Yu Chun; Wu, Xiaoyun; Kappes, John C.; Towler, Eric M.

doi:10.1089/088922200750054701

Cited by 23 publications

(17 citation statements)

References 22 publications

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“…Active site mutant of full-length HERV-K10 protease was not enzymatically active, as expected. These results seem to be consistent with differential cleavage of HIV-1 Gag and Pol precursors by HERV-K10 protease in the context of chimeric virions, where the HERV enzyme cleaved HIV-1 polyproteins at both apparently authentic as well as nonauthentic sites (17,38).…”

Section: Expression and Purification Of Herv-k10supporting

confidence: 75%

“…The existence of a functional HERV-K protease was inferred from the presence of processed Gag proteins in teratocarcinoma cells (5). Direct evidence for a functional protease activity came from expression of different clones in E. coli (15,17,25,38).…”

Section: Discussionmentioning

confidence: 99%

“…Whether it is the full-length enzyme that is biologically relevant or additional C-terminal processing occurs to give rise to smaller molecular species remains to be seen. Initial studies suggest that some limited cleavage of 13 amino acid residues at the C terminus occurs after prolonged incubation (25,38).…”

Section: Discussionmentioning

confidence: 99%

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Inhibition of Human Endogenous Retrovirus-K10 Protease in Cell-free and Cell-based Assays

Kuhelj¹,

Rizzo²,

Chang

et al. 2001

Journal of Biological Chemistry

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A full-length and C-terminally truncated version of human endogenous retrovirus (HERV)-K10 protease were expressed in Escherichia coli and purified to homogeneity. Both versions of the protease efficiently processed HERV-K10 Gag polyprotein substrate. HERV-K10 Gag was also cleaved by human immunodeficiency virus, type 1 (HIV-1) protease, although at different sites. To identify compounds that could inhibit protein processing dependent on the HERV-K10 protease, a series of cyclic ureas that had previously been shown to inhibit HIV-1 protease was tested. Several symmetric bisamides acted as very potent inhibitors of both the truncated and full-length form of HERV-K10 protease, in subnanomolar or nanomolar range, respectively. One of the cyclic ureas, SD146, can inhibit the processing of in vitro translated HERV-K10 Gag polyprotein substrate by HERV-K10 protease. In addition, in virus-like particles isolated from the teratocarcinoma cell line NCCIT, there is significant accumulation of Gag and Gag-Pol precursors upon treatment with SD146, suggesting the compound efficiently blocks HERV-K Gag processing in cells. This is the first report of an inhibitor able to block cell-associated processing of Gag polypeptides of an endogenous retrovirus.

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Section: Expression and Purification Of Herv-k10supporting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

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Inhibition of Human Endogenous Retrovirus-K10 Protease in Cell-free and Cell-based Assays

Kuhelj¹,

Rizzo²,

Chang

et al. 2001

Journal of Biological Chemistry

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“…The HIV-1 protease, for example, can cleave HERV-K Gag (96,126). In addition, HIV-1 Rev can actively transport HERV-K RNA from the nucleus to the cytoplasm of cells that express it (135).…”

Section: Discussionmentioning

confidence: 99%

Expression of Human Endogenous Retrovirus Type K (HML-2) Is Activated by the Tat Protein of HIV-1

Gonzalez-Hernandez

Swanson

Contreras-Galindo

et al. 2012

J Virol

107

128

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“…The viral particles present in plasma may be a result of ongoing productive infection, release of viral particles from latently infected cells, or both. Indirect evidence for ongoing productive infection includes the presence of HIV RNA in cells (20,32,35), viral evolution (24), and rapid rebound of virus after therapy interruption (13,14,49). Conversely, the presence of drug-sensitive, archival virus in patients responding to potent antiretroviral regimens suggests that productive infection contributes little to residual viremia (26).…”

mentioning

confidence: 99%

Productive Infection Maintains a Dynamic Steady State of Residual Viremia in Human Immunodeficiency Virus Type 1-Infected Persons Treated with Suppressive Antiretroviral Therapy for Five Years

Havlir

Strain²,

Clerici³

et al. 2003

J Virol

138

132

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To provide insight into the dynamics and source of residual viremia in human immunodeficiency virus (HIV) patients successfully treated with antiretroviral therapy, 14 intensely monitored patients treated with indinavir and efavirenz sustaining HIV RNA at <50 copies/ml for >5 years were studied. Abacavir was added to the regimen of eight patients at year 5. After the first 9 months of therapy, HIV RNA levels had reached a plateau ("residual viremia") that persisted for over 5 years. Levels of residual viremia differed among patients and ranged from 3.2 to 23 HIV RNA copies/ml. Baseline HIV DNA was the only significant pretreatment predictor of residual viremia in regression models including baseline HIV RNA, CD4 count, and patient age. In the four of five patients with detectable viremia who added abacavir to their regimen after 5 years, HIV RNA levels declined rapidly. The estimated half-life of infected cells was 6.7 days. Decrease in activated memory cells and a reduction in gamma interferon production to HIV Gag and p24 antigen in ELISpot assays were observed, consistent with a decrease in HIV replication. Thus, in patients treated with efavirenz plus indinavir, levels of residual viremia were established by 9 months, were predicted by baseline proviral DNA, and remained constant for 5 years. Even after years of highly suppressive therapy, HIV RNA levels declined rapidly after the addition of abacavir, suggesting that productive infection contributes to residual ongoing viremia and can be inhibited with therapy intensification.

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Analysis of Human Immunodeficiency Virus Type 1 Containing HERV-K Protease

Cited by 23 publications

References 22 publications

Inhibition of Human Endogenous Retrovirus-K10 Protease in Cell-free and Cell-based Assays

Inhibition of Human Endogenous Retrovirus-K10 Protease in Cell-free and Cell-based Assays

Expression of Human Endogenous Retrovirus Type K (HML-2) Is Activated by the Tat Protein of HIV-1

Productive Infection Maintains a Dynamic Steady State of Residual Viremia in Human Immunodeficiency Virus Type 1-Infected Persons Treated with Suppressive Antiretroviral Therapy for Five Years

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