Page last updated: 2024-10-24
establishment of integrated proviral latency
Definition
Target type: biologicalprocess
A process by which the virus integrates into the host genome and establishes as a stable provirus or prophage. [GOC:jl]
Integrated proviral latency, the state of a dormant HIV-1 provirus integrated into the host cell's genome, is established through a complex interplay of viral and host factors. The process begins with viral entry and fusion into the target cell, typically a CD4+ T lymphocyte. Once inside, the viral RNA genome is reverse transcribed into DNA by the viral enzyme reverse transcriptase. This DNA copy then enters the nucleus and integrates into the host cell's genome, becoming a provirus. This integration is mediated by the viral enzyme integrase. After integration, the provirus remains dormant, not actively producing new viral particles. This latency is maintained through a combination of factors, including:
1. Chromatin modifications: The proviral DNA can be packaged in a tightly compacted state, preventing transcription of viral genes.
2. Transcriptional repression: Cellular transcription factors can bind to the proviral DNA and block transcription.
3. Post-transcriptional silencing: Viral mRNAs can be targeted for degradation by host cell machinery.
4. Viral protein interactions: Viral proteins can interact with host cell proteins to suppress viral gene expression.
This latency state is crucial for HIV-1 persistence, as it allows the virus to evade the host's immune system and antiviral therapies. However, latency is not static, and the provirus can be reactivated under certain conditions, leading to the production of new viral particles and the spread of infection. Factors that can reactivate HIV-1 from latency include:
1. Immune activation: Stimulation of the immune system can activate proviral transcription.
2. Cellular stress: Exposure to toxins or other stressors can lead to reactivation.
3. Certain drugs: Some medications can induce viral reactivation.
Understanding the mechanisms of proviral latency and reactivation is critical for developing effective antiretroviral therapies and cure strategies for HIV-1 infection.'
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Proteins (1)
| Protein | Definition | Taxonomy |
|---|---|---|
| Gag-Pol polyprotein | A lentivirus-type gag-pol polyprotein that is encoded in the genome of human immunodeficiency virus type 1 group M subtype B (isolate HXB2). [PRO:DAN] | HIV-1 M:B_HXB2R |
Compounds (50)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| ag-1549 | capravirine: a non-nucleoside reverse transcriptase inhibitor | ||
| nevirapine | nevirapine : A dipyridodiazepine that is 5,11-dihydro-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepine which is substituted by methyl, oxo, and cyclopropyl groups at positions 4, 6, and 11, respectively. A non-nucleoside reverse transcriptase inhibitor with activity against HIV-1, it is used in combination with other antiretrovirals for the treatment of HIV infection. Nevirapine: A potent, non-nucleoside reverse transcriptase inhibitor used in combination with nucleoside analogues for treatment of HIV INFECTIONS and AIDS. | cyclopropanes; dipyridodiazepine | antiviral drug; HIV-1 reverse transcriptase inhibitor |
| delavirdine | delavirdine : The amide resulting from the formal condensation of 5-[(methylsulfonyl)amino]-1H-indole-2-carboxylic acid and 4-amino group of 1-[3-(isopropylamino)pyridin-2-yl]piperazine, delavirdine is a non-nucleoside reverse transcriptase inhibitor with activity specific for HIV-1. Viral resistance emerges rapidly when delavirdine is used alone, so it is therefore used (as the methanesulfonic acid salt) with other antiretrovirals for combination therapy of HIV infection. Delavirdine: A potent, non-nucleoside reverse transcriptase inhibitor with activity specific for HIV-1. | aminopyridine; indolecarboxamide; N-acylpiperazine; sulfonamide | antiviral drug; HIV-1 reverse transcriptase inhibitor |
| alizarin | dihydroxyanthraquinone | chromophore; dye; plant metabolite | |
| methylamine | methyl group : An alkyl group that is the univalent group derived from methane by removal of a hydrogen atom. | methylamines; one-carbon compound; primary aliphatic amine | mouse metabolite |
| l 697639 | L 697639: structure given in first source | ||
| atevirdine | atevirdine: inhibits replication of HIV-1; U 87201E is the methanesulfonate salt | ||
| efavirenz | efavirenz : 1,4-Dihydro-2H-3,1-benzoxazin-2-one substituted at the 4 position by cyclopropylethynyl and trifluoromethyl groups (S configuration) and at the 6 position by chlorine. A non-nucleoside reverse transcriptase inhibitor with activity against HIV, it is used with other antiretrovirals for combination therapy of HIV infection. efavirenz: HIV-1 reverse transcriptase inhibitor | acetylenic compound; benzoxazine; cyclopropanes; organochlorine compound; organofluorine compound | antiviral drug; HIV-1 reverse transcriptase inhibitor |
| nelfinavir | nelfinavir : An aryl sulfide that is used (as its mesylate salt) for treatment of HIV and also exhibits some anticancer properties. Nelfinavir: A potent HIV protease inhibitor. It is used in combination with other antiviral drugs in the treatment of HIV in both adults and children. | aryl sulfide; benzamides; organic heterobicyclic compound; phenols; secondary alcohol; tertiary amino compound | antineoplastic agent; HIV protease inhibitor |
| nsc 624231 | 2'-nitrophenylphenylsulfone: inhibits HIV-1 reverse transcriptase; structure given in first source | ||
| 1-((2-hydroxyethoxy)methyl)-6-(phenylthio)thymine | 1-[(2-hydroxyethoxy)methyl]-6-(phenylsulfanyl)thymine : A pyrimidone that is thymine which is substituted at positions 1 and 6 by a (2-hydroxyethoxy)methyl group and a phenylsulfanyl group, respectively. | aryl sulfide; primary alcohol; pyrimidone | antiviral drug; HIV-1 reverse transcriptase inhibitor |
| l 693593 | L 693593: structure given in first source | ||
| l-697661 | L-697661: HIV-1 reverse transcriptase inhibitor | ||
| emivirine | emivirine : A pyrimidone that is uracil which is substituted at positions 1, 5 and 6 by ethoxymethyl, isopropyl, and benzyl groups, respectively. A non-nucleoside inhibitor of HIV-1 reverse transcriptase, emivirine was an unsuccessful experimental agent for the treatment of HIV. emivirine: a non-nucleoside inhibitor of HIV-1 reverse transcriptase | pyrimidone | antiviral drug; HIV-1 reverse transcriptase inhibitor |
| amprenavir | carbamate ester; sulfonamide; tetrahydrofuryl ester | antiviral drug; HIV protease inhibitor | |
| 4-fluorobenzylamine | |||
| u 88204 | U 88204: structure given in first source | ||
| beta-thujaplicinol | beta-thujaplicinol: inhibits ribonuclease H activity of HIV-1 reverse transcriptase; structure in first source | ||
| 4-methoxybenzylamine | 1-(4-methoxyphenyl)methanamine : An aralkylamino compound that is benzylamine substituted by a methoxy group at the para position. | aralkylamino compound; aromatic ether; primary amino compound | |
| 1-(2',6'-difluorophenyl)-1h,3h-thiazolo(3,4-a)benzimidazole | 1-(2',6'-difluorophenyl)-1H,3H-thiazolo(3,4-a)benzimidazole: anti-HIV agent; a non-nucleoside reverse transcriptase inhibitor; structure given in first source | ||
| l 696040 | L 696040: structure given in first source | ||
| dmp 450 | DMP 450: structure in first source | ||
| gw420867x | GW420867X: structure in first source | ||
| l 734005 | 5-chloro-3-phenylthioindole-2-carboxamide: structure given in first source; an inhibitor of HIV-1 reverse transcriptase | ||
| 2-benzyloxybenzaldehyde | |||
| ritonavir | ritonavir : An L-valine derivative that is L-valinamide in which alpha-amino group has been acylated by a [(2-isopropyl-1,3-thiazol-4-yl)methyl]methylcarbamoyl group and in which a hydrogen of the carboxamide amino group has been replaced by a (2R,4S,5S)-4-hydroxy-1,6-diphenyl-5-{[(1,3-thiazol-5-ylmethoxy)carbonyl]amino}hexan-2-yl group. A CYP3A inhibitor and antiretroviral drug from the protease inhibitor class used to treat HIV infection and AIDS, it is often used as a fixed-dose combination with another protease inhibitor, lopinavir. Also used in combination with dasabuvir sodium hydrate, ombitasvir and paritaprevir (under the trade name Viekira Pak) for treatment of chronic hepatitis C virus genotype 1 infection as well as cirrhosis of the liver. Ritonavir: An HIV protease inhibitor that works by interfering with the reproductive cycle of HIV. It also inhibits CYTOCHROME P-450 CYP3A. | 1,3-thiazoles; carbamate ester; carboxamide; L-valine derivative; ureas | antiviral drug; environmental contaminant; HIV protease inhibitor; xenobiotic |
| adam ii | ADAM II: an alkenyldiarylmethane compound; structure in first source | ||
| saquinavir | saquinavir : An aspartic acid derivative obtained by formal condensation of the primary amino group of (2S,3R)-4-[(3S,4aS,8aS)-3-(tert-butylcarbamoyl)octahydroisoquinolin-2(1H)-yl]-3-hydroxy-1-phenylbutan-2-ylamine with the carboxy group of N(2)(-quinolin-2-ylcarbonyl)-L-asparagine. An inhibitor of HIV-1 protease. Saquinavir: An HIV protease inhibitor which acts as an analog of an HIV protease cleavage site. It is a highly specific inhibitor of HIV-1 and HIV-2 proteases, and also inhibits CYTOCHROME P-450 CYP3A. | L-asparagine derivative; quinolines | antiviral drug; HIV protease inhibitor |
| a 76928 | A 76928: a diol with C2-symmetry | ||
| je 2147 | |||
| l 737126 | 5-chloro-3-(phenylsulfonyl)indole-2-carboxamide: structure given in first source; an inhibitor of HIV-1 reverse transcriptase | ||
| bevirimat | bevirimat : A pentacyclic triterpenoid obtained by the formal condensation of 2,2-dimethylsuccinic acid with the 3-hydroxy group of betulinic acid. It is isolated from the Chinese herb Syzygium claviflorum. The first in the class of HIV-1 maturation inhibitors to be studied in humans, bevirimat was identified as a potent HIV drug candidate and several clinical trials were conducted, but development into a new drug was plagued by numerous resistance-related problems. bevirimat: an HIV inhibitor; disrupts late step in processing HIV Major Core Protein p24, preventing the capsid precursor p25 from being converted to mature capsid p24 | dicarboxylic acid monoester; monocarboxylic acid; pentacyclic triterpenoid | HIV-1 maturation inhibitor; metabolite |
| 5-(1,1-dioxido-1,2-thiazinan-2-yl)-n-(4-fluorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide | 5-(1,1-dioxido-1,2-thiazinan-2-yl)-N-(4-fluorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide: structure in first source | ||
| dpc 961 | |||
| l 731988 | L 731988: structure in first source | ||
| l 708906 | |||
| 3-dimethylamino-4-(3,5-dimethylbenzyl)-5-ethyl-6-methylpyridin-2(1h)-one | 3-dimethylamino-4-(3,5-dimethylbenzyl)-5-ethyl-6-methylpyridin-2(1H)-one: structure in first source | ||
| r-82913 | R-82913: antiviral target on reverse transcriptase of HIV-1 | ||
| hby 097 | HBY 097: a quinoxaline derivative | ||
| trovirdine | trovirdine: HIV-1 reverse transcriptase inhibitor | ||
| ly 73497 | LY 73497: HIV-1 reverse transcriptase inhibitor; structure in first source | ||
| dpc 083 | |||
| indinavir sulfate | Indinavir: A potent and specific HIV protease inhibitor that appears to have good oral bioavailability. | dicarboxylic acid diamide; N-(2-hydroxyethyl)piperazine; piperazinecarboxamide | HIV protease inhibitor |
| l 682679 | L 682679: structure given in first source | ||
| brecanavir | brecanavir: HIV protease inhibitor | ||
| rilpivirine | aminopyrimidine; nitrile | EC 2.7.7.49 (RNA-directed DNA polymerase) inhibitor; HIV-1 reverse transcriptase inhibitor | |
| n-(4-fluorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide | N-(4-fluorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide: HIV-1 integrase inhibitor; structure in first source | ||
| raltegravir | 1,2,4-oxadiazole; dicarboxylic acid amide; hydroxypyrimidine; monofluorobenzenes; pyrimidone; secondary carboxamide | antiviral drug; HIV-1 integrase inhibitor | |
| tipranavir | tipranavir : A pyridine-2-sulfonamide substituted at C-5 by a trifluoromethyl group and at the sulfonamide nitrogen by a dihydropyrone-containing m-tolyl substituent. It is an HIV-1 protease inhibitor. tipranavir: inhibits HIV-1 protease | sulfonamide | antiviral drug; HIV protease inhibitor |
| 2-(methylthio)-6-(phenylmethyl)-1H-pyrimidin-4-one | aryl sulfide |