Retroviral Integration
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Retroviral Integration
The pre-integration complex (PIC) is a nucleoprotein complex of viral genetic material and associated viral and host proteins which is capable of inserting a viral genome into a host genome. The PIC forms after uncoating of a viral particle after entry into the host cell. In the case of the human immunodeficiency virus (HIV), the PIC forms after the Reverse Transcription Complex (RTC) has reverse transcribed the viral RNA into DNA. The PIC consists of viral proteins (including Vpr, matrix and integrase), host proteins (including Barrier to autointegration factor 1) and the viral DNA. The PIC enters the cellular nucleus through the nuclear pore complex without disrupting the nuclear envelope, thus allowing HIV and related retroviruses to replicate in non-dividing cells. Following nuclear entry, the PIC's DNA payload may be integrated into the host DNA as a " provirus". See also * HIV *Barrier to autointegration factor 1 Barrier-to-autointegration factor is a protein tha ...
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Nucleoprotein
Nucleoproteins are proteins conjugated with nucleic acids (either DNA or RNA). Typical nucleoproteins include ribosomes, nucleosomes and viral nucleocapsid proteins. Structures Nucleoproteins tend to be positively charged, facilitating interaction with the negatively charged nucleic acid chains. The tertiary structures and biological functions of many nucleoproteins are understood.Graeme K. Hunter G. K. (2000): Vital Forces. The discovery of the molecular basis of life. Academic Press, London 2000, . Important techniques for determining the structures of nucleoproteins include X-ray diffraction, nuclear magnetic resonance and cryo-electron microscopy. Viruses Virus genomes (either DNA or RNA) are extremely tightly packed into the viral capsid. Many viruses are therefore little more than an organised collection of nucleoproteins with their binding sites pointing inwards. Structurally characterised viral nucleoproteins include influenza, rabies, Ebola, Bunyamwera, Schmal ...
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Genetic Material
Nucleic acids are biopolymers, macromolecules, essential to all known forms of life. They are composed of nucleotides, which are the monomers made of three components: a 5-carbon sugar, a phosphate group and a nitrogenous base. The two main classes of nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). If the sugar is ribose, the polymer is RNA; if the sugar is the ribose derivative deoxyribose, the polymer is DNA. Nucleic acids are naturally occurring chemical compounds that serve as the primary information-carrying molecules in cells and make up the genetic material. Nucleic acids are found in abundance in all living things, where they create, encode, and then store information of every living cell of every life-form on Earth. In turn, they function to transmit and express that information inside and outside the cell nucleus to the interior operations of the cell and ultimately to the next generation of each living organism. The encoded information is co ...
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Viral Matrix Protein
Viral matrix proteins are structural proteins linking the viral envelope with the virus core. They play a crucial role in virus assembly, and interact with the RNP complex as well as with the viral membrane. They are found in many enveloped viruses including paramyxoviruses, orthomyxoviruses, herpesviruses, retroviruses, filoviruses and other groups. An example is the M1 protein of the influenza virus, showing affinity to the glycoproteins inserted in the host cell membrane on one side and affinity for the RNP complex molecules on the other side, which allows formation at the membrane of a complex made of the viral ribonucleoprotein at the inner side indirectly connected to the viral glycoproteins protruding from the membrane. This assembly complex will now bud out of the cell as new mature viruses. Viral matrix proteins, like many other viral proteins, can exert different functions during the course of the infection. For example, in rhabdoviruses, binding of M proteins to nuc ...
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Integrase
Retroviral integrase (IN) is an enzyme produced by a retrovirus (such as HIV) that integrates—forms covalent links between—its genetic information into that of the host cell it infects. Retroviral INs are not to be confused with phage integrases (recombinases) used in biotechnology, such as λ phage integrase, as discussed in site-specific recombination. The macromolecular complex of an IN macromolecule bound to the ends of the viral DNA ends has been referred to as the '' intasome''; IN is a key component in this and the retroviral pre-integration complex. Structure All retroviral IN proteins contain three canonical domains, connected by flexible linkers: ● an N-terminal HH-CC zinc-binding domain (a three-helical bundle stabilized by coordination of a Zn(II) cation) ● a catalytic core domain (RNaseH fold) ● a C-terminal DNA-binding domain ( SH3 fold). Crystal and NMR structures of the individual domains and 2-domain constructs of integrase ...
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Barrier To Autointegration Factor 1
Barrier-to-autointegration factor is a protein that in humans is encoded by the ''BANF1'' gene. It is a member of the barrier-to-autointegration factor family of proteins. Function The protein encoded by this gene was identified by its ability to protect retroviruses from intramolecular integration and therefore promote intermolecular integration into the host cell genome. The endogenous function of the protein is unknown. The protein forms a homodimer which localizes to the nucleus and is specifically associated with chromosomes during mitosis. This protein binds to DNA in a non-specific manner and studies in rodents suggest that it also binds to lamina-associated polypeptide 2, a component of the nuclear lamina. It also associates with the LEM Domain containing proteins LAP2, Emerin, and MAN1. The protein's DNA binding ability is modulated by ATP concentration. Interactions Barrier to autointegration factor 1 has been shown to interact with Thymopoietin Lamina-asso ...
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Nuclear Pore Complex
A nuclear pore is a part of a large complex of proteins, known as a nuclear pore complex that spans the nuclear envelope, which is the double membrane surrounding the eukaryotic cell nucleus. There are approximately 1,000 nuclear pore complexes (NPCs) in the nuclear envelope of a vertebrate cell, but this number varies depending on cell type and the stage in the life cycle. The human nuclear pore complex (hNPC) is a 110 megadalton (MDa) structure. The proteins that make up the nuclear pore complex are known as nucleoporins; each NPC contains at least 456 individual protein molecules and is composed of 34 distinct nucleoporin proteins. About half of the nucleoporins typically contain solenoid protein domains—either an alpha solenoid or a beta-propeller fold, or in some cases both as separate structural domains. The other half show structural characteristics typical of "natively unfolded" or intrinsically disordered proteins, i.e. they are highly flexible proteins that lack ...
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Nuclear Envelope
The nuclear envelope, also known as the nuclear membrane, is made up of two lipid bilayer membranes that in eukaryotic cells surround the nucleus, which encloses the genetic material. The nuclear envelope consists of two lipid bilayer membranes: an inner nuclear membrane and an outer nuclear membrane. The space between the membranes is called the perinuclear space. It is usually about 10–50 nm wide. The outer nuclear membrane is continuous with the endoplasmic reticulum membrane. The nuclear envelope has many nuclear pores that allow materials to move between the cytosol and the nucleus. Intermediate filament proteins called lamins form a structure called the nuclear lamina on the inner aspect of the inner nuclear membrane and give structural support to the nucleus. Structure The nuclear envelope is made up of two lipid bilayer membranes, an inner nuclear membrane and an outer nuclear membrane. These membranes are connected to each other by nuclear pores. Two sets o ...
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Retroviruses
A retrovirus is a type of virus that inserts a DNA copy of its RNA genome into the DNA of a host cell that it invades, thus changing the genome of that cell. Once inside the host cell's cytoplasm, the virus uses its own reverse transcriptase enzyme to produce DNA from its RNA genome, the reverse of the usual pattern, thus ''retro'' (backwards). The new DNA is then incorporated into the host cell genome by an integrase enzyme, at which point the retroviral DNA is referred to as a provirus. The host cell then treats the viral DNA as part of its own genome, transcribing and translating the viral genes along with the cell's own genes, producing the proteins required to assemble new copies of the virus. Although retroviruses have different subfamilies, they have three basic groups: the oncoretroviruses (oncogenic retroviruses), the lentiviruses (slow retroviruses) and the spumaviruses (foamy viruses). The oncoretroviruses are able to cause cancer in some species, the lentiv ...
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Provirus
A provirus is a virus genome that is integrated into the DNA of a host cell. In the case of bacterial viruses (bacteriophages), proviruses are often referred to as prophages. However, proviruses are distinctly different from prophages and these terms should not be used interchangeably. Unlike prophages, proviruses do not excise themselves from the host genome when the host cell is stressed. This state can be a stage of virus replication, or a state that persists over longer periods of time as either inactive viral infections or an endogenous viral element. In inactive viral infections the virus will not replicate itself except through replication of its host cell. This state can last over many host cell generations. Endogenous retroviruses are always in the state of a provirus. When a (nonendogenous) retrovirus invades a cell, the RNA of the retrovirus is reverse-transcribed into DNA by reverse transcriptase, then inserted into the host genome by an integrase. A provirus does ...
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