''Lentivirus'' is a
genus
Genus (; : genera ) is a taxonomic rank above species and below family (taxonomy), family as used in the biological classification of extant taxon, living and fossil organisms as well as Virus classification#ICTV classification, viruses. In bino ...
of
retrovirus
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. After invading a host cell's cytoplasm, the virus uses its own reverse transcriptase e ...
es that cause chronic and deadly diseases characterized by long
incubation period
Incubation period (also known as the latent period or latency period) is the time elapsed between exposure to a pathogenic organism, a chemical, or ionizing radiation, radiation, and when symptoms and signs are first apparent. In a typical infect ...
s, in humans and other mammalian species.
The genus includes the
human immunodeficiency virus
The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause AIDS, acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of th ...
(HIV), which causes
AIDS
The HIV, human immunodeficiency virus (HIV) is a retrovirus that attacks the immune system. Without treatment, it can lead to a spectrum of conditions including acquired immunodeficiency syndrome (AIDS). It is a Preventive healthcare, pr ...
. Lentiviruses are distributed worldwide, and are known to be hosted in apes,
cows
Cattle (''Bos taurus'') are large, domesticated, bovid ungulates widely kept as livestock. They are prominent modern members of the subfamily Bovinae and the most widespread species of the genus '' Bos''. Mature female cattle are called co ...
, goats, horses, cats, and sheep as well as several other mammals.
Lentiviruses can integrate a significant amount of
viral complementary DNA
In genetics, complementary DNA (cDNA) is DNA that was reverse transcribed (via reverse transcriptase) from an RNA (e.g., messenger RNA or microRNA). cDNA exists in both single-stranded and double-stranded forms and in both natural and engin ...
into the
DNA
Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...
of the
host cell
In biology and medicine, a host is a larger organism that harbours a smaller organism; whether a parasitic, a mutualistic, or a commensalist ''guest'' (symbiont). The guest is typically provided with nourishment and shelter. Examples include ...
and can efficiently infect nondividing cells, so they are one of the most efficient methods of
gene delivery
Gene delivery is the process of introducing foreign genetic material, such as DNA or RNA, into host cells. Gene delivery must reach the genome of the host cell to induce gene expression. Successful gene delivery requires the foreign gene deliver ...
. They can become
endogenous
Endogeny, in biology, refers to the property of originating or developing from within an organism, tissue, or cell.
For example, ''endogenous substances'', and ''endogenous processes'' are those that originate within a living system (e.g. an ...
, integrating their genome into the host
germline
In biology and genetics, the germline is the population of a multicellular organism's cells that develop into germ cells. In other words, they are the cells that form gametes ( eggs and sperm), which can come together to form a zygote. They dif ...
genome, so that the virus is henceforth inherited by the host's descendants.
Classification
Five
serogroups of lentiviruses are recognized, reflecting the vertebrate hosts with which they are associated (primates, sheep and goats, horses, domestic cats, and cattle). The
primate
Primates is an order (biology), order of mammals, which is further divided into the Strepsirrhini, strepsirrhines, which include lemurs, galagos, and Lorisidae, lorisids; and the Haplorhini, haplorhines, which include Tarsiiformes, tarsiers a ...
lentiviruses are distinguished by the use of
CD4
In molecular biology, CD4 (cluster of differentiation 4) is a glycoprotein that serves as a co-receptor for the T-cell receptor (TCR). CD4 is found on the surface of immune cells such as helper T cells, monocytes, macrophages, and dendritic c ...
protein as a
receptor
Receptor may refer to:
* Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse
*Receptor (biochemistry), in biochemistry, a protein molecule that receives and respond ...
and the absence of
dUTPase. Some groups have cross-reactive gags (
group-specific antigen
Group-specific antigen, or gag, is the polyprotein that contains the core structural proteins of an Ortervirus (except ''Caulimoviridae''). It was named as such because scientists used to believe it was antigenic. Now it is known that it makes u ...
s) (e.g., the
ovine
Sheep (: sheep) or domestic sheep (''Ovis aries'') are a domesticated, ruminant mammal typically kept as livestock. Although the term ''sheep'' can apply to other species in the genus ''Ovis'', in everyday usage it almost always refers to dom ...
,
caprine, and
feline lentiviruses).
Antibodies
An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses, including those that caus ...
to gags in lions and other large felines indicate the existence of another yet-to-be identified virus related to feline lentivirus and the ovine/caprine lentiviruses.
The genus contains the following species, listed by scientific name and followed by the exemplar virus of the species:
* ''Lentivirus bovimdef'',
Bovine immunodeficiency virus
Bovine immunodeficiency virus (BIV) is a retrovirus belonging to the genus '' Lentivirus''. It is similar to the human immunodeficiency virus (HIV) and infects cattle. The cells primarily infected are lymphocytes and monocytes/macrophages.
D ...
* ''Lentivirus bovjem'',
Jembrana disease virus
Jembrana disease is an acute viral disease of cattle. While it produces relatively mild symptoms in taurine cattle, the Jembrana virus is particularly severe in Bali cattle where it has a fatality rate of approximately 17 percent. Its first docu ...
* ''Lentivirus capartenc'',
Caprine arthritis encephalitis virus
Caprine arthritis encephalitis virus (CAEV) is a retrovirus which infects goats and cross-reacts immunologically with HIV, due to being from the same family of viruses. CAEV cannot be transmitted to humans, including through the consumption of m ...
* ''Lentivirus equinfane'',
Equine infectious anemia virus
Equine infectious anemia or equine infectious anaemia (EIA), also known by horsemen as swamp fever, is a horse disease caused by a retrovirus (Equine infectious anemia virus) and transmitted by bloodsucking insects. The virus (EIAV) is endemic in ...
* ''Lentivirus felimdef'',
Feline immunodeficiency virus
Feline immunodeficiency virus (FIV) is a lentivirus that affects cats worldwide and 2.5% to 4.4% of felines are infected.
FIV was first isolated in 1986, by Niels C. Pedersen and Janet K. Yamamoto at the UC Davis School of Veterinary Med ...
* ''Lentivirus humimdef1'',
Human immunodeficiency virus 1
The subtypes of HIV include two main subtypes, known as HIV type 1 (HIV-1) and HIV type 2 (HIV-2). These subtypes have distinct genetic differences and are associated with different Epidemiology, epidemiological patterns and clinical characteristi ...
* ''Lentivirus humimdef2'',
Human immunodeficiency virus 2
The subtypes of HIV include two main subtypes, known as HIV type 1 (HIV-1) and HIV type 2 (HIV-2). These subtypes have distinct genetic differences and are associated with different epidemiological patterns and clinical characteristics.
HIV-1 e ...
* ''Lentivirus ovivismae'',
Visna/maedi virus
* ''Lentivirus pum'',
Puma lentivirus
Puma lentivirus (PLV) is a retrovirus in the genus ''Lentivirus
''Lentivirus'' is a genus of retroviruses that cause chronic and deadly diseases characterized by long incubation periods, in humans and other mammalian species. The genus includ ...
* ''Lentivirus simimdef'',
Simian immunodeficiency virus
Simian immunodeficiency virus (SIV) is a species of retrovirus that cause persistent infections in at least 45 species of non-human primates. Based on analysis of strains found in four species of monkeys from Bioko Island, which was isolated fr ...
Morphology

The
virions
A virion (plural, ''viria'' or ''virions'') is an inert virus particle capable of invading a cell. Upon entering the cell, the virion disassembles and the genetic material from the virus takes control of the cell infrastructure, thus enabling th ...
are enveloped viruses 80–100 nm in diameter.
[ They are spherical or pleomorphic, with capsid cores that mature to a cylindrical or conical shape.] Projections of envelope
An envelope is a common packaging item, usually made of thin, flat material. It is designed to contain a flat object, such as a letter (message), letter or Greeting card, card.
Traditional envelopes are made from sheets of paper cut to one o ...
make the surface appear rough, or tiny spikes
The SPIKES protocol is a method used in clinical medicine to break bad news to patients and families. As receiving bad news can cause distress and anxiety, clinicians need to deliver the news carefully. Using the SPIKES method for introducing and ...
(about 8 nm) may be dispersed evenly over the surface.
Genome
Lentiviruses contain 2 positive sense, single-strand RNAs that are bound by nucleocapsid proteins. As with all retroviruses, lentiviruses have ''gag'', ''pol'' and ''env'' genes, coding for viral proteins in the order: 5´-''gag''-''pol''-''env''-3´. Unlike other retroviruses, however, lentiviruses have two regulatory genes, ''tat'' and ''rev''. They may also have additional accessory genes depending on the virus (e.g., for HIV-1: ''vif'', ''vpr
Vpr is a Human immunodeficiency virus gene and protein product. Vpr stands for "Viral Protein R". Vpr, a 96 amino acid 14-kDa protein, plays an important role in regulating nuclear import of the HIV-1 pre-integration complex, and is required for ...
'', '' vpu'', ''nef'') whose products are involved in regulation of synthesis and processing viral RNA and other replicative functions. The long terminal repeat
A long terminal repeat (LTR) is a pair of identical sequences of DNA, several hundred base pairs long, which occur in eukaryotic genomes on either end of a series of genes or pseudogenes that form a retrotransposon or an endogenous retrovirus o ...
(LTR) is about 600 nt long, of which the U3 region is 450, the R sequence 100 and the U5 region some 70 nt long.
Replication
Retroviruses carry proteins within their capsid
A capsid is the protein shell of a virus, enclosing its genetic material. It consists of several oligomeric (repeating) structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or m ...
s, which bind the RNA genome. These proteins are typically involved in the early stages of genome replication, and include reverse transcriptase
A reverse transcriptase (RT) is an enzyme used to convert RNA genome to DNA, a process termed reverse transcription. Reverse transcriptases are used by viruses such as HIV and hepatitis B to replicate their genomes, by retrotransposon mobi ...
and integrase
Retroviral integrase (IN) is an enzyme
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme ...
. Reverse transcriptase is the virally encoded RNA-dependent DNA polymerase. The enzyme uses the viral RNA genome as a template for the synthesis of a complementary DNA copy. Reverse transcriptase possesses Nase Hactivity for destruction of the RNA-template. Integrase binds both the viral cDNA generated by reverse transcriptase and the host DNA. It then processes the LTRs before inserting the viral genome into the host DNA. Tat acts as a trans-activator during transcription to enhance initiation and elongation. The Rev responsive element acts post-transcriptionally, regulating mRNA splicing and transport to the cytoplasm.
Proteome
The lentiviral proteome consists of five major structural proteins and three or four non-structural proteins. Primate lentiviruses lack the dUTPase, so they have three non-structural proteins, whereas all other lentiviruses encode it.
Structural proteins listed by size:
# Gp120
Envelope glycoprotein GP120 (or gp120) is a glycoprotein exposed on the surface of the HIV envelope. It was discovered by Professors Tun-Hou Lee and Myron "Max" Essex of the Harvard School of Public Health in 1984. The 120 in its name comes f ...
surface envelope protein SU, encoded by the viral gene '' env''. 120000 Da ( daltons).
# Gp41
Gp41 also known as glycoprotein 41 is a subunit of the envelope protein complex of retroviruses, including human immunodeficiency virus (HIV). Gp41 is a transmembrane protein that contains several sites within its ectodomain that are required fo ...
transmembrane envelope protein TM, also encoded by the viral gene ''env''. 41000 Da.
# P24 capsid
A capsid is the protein shell of a virus, enclosing its genetic material. It consists of several oligomeric (repeating) structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or m ...
protein CA, encoded by the viral gene ''gag''. 24000 Da.
# P17 matrix
Matrix (: matrices or matrixes) or MATRIX may refer to:
Science and mathematics
* Matrix (mathematics), a rectangular array of numbers, symbols or expressions
* Matrix (logic), part of a formula in prenex normal form
* Matrix (biology), the m ...
protein MA, also encoded by ''gag''. 17000 Da.
# P7/P9 capsid protein NC, also encoded by ''gag''. 7000–11000 Da.
The envelope proteins SU and TM are glycosylated
Glycosylation is the reaction in which a carbohydrate (or ' glycan'), i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule (a glycosyl acceptor) in order to form a glycoconjugate. In biology (but not ...
in at least some lentiviruses (HIV, SIV), if not all of them. Glycosylation seems to play a structural role in the concealment and variation of antigenic sites necessary for the host to mount an immune system response.
Enzymes:
# Reverse transcriptase
A reverse transcriptase (RT) is an enzyme used to convert RNA genome to DNA, a process termed reverse transcription. Reverse transcriptases are used by viruses such as HIV and hepatitis B to replicate their genomes, by retrotransposon mobi ...
RT encoded by the ''pol'' gene. Protein size 66000 Da.
# Integrase
Retroviral integrase (IN) is an enzyme
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme ...
IN also encoded by the ''pol'' gene. Protein size 32000 Da.
# Protease
A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalysis, catalyzes proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the formation of new protein products ...
PR encoded by the ''pro'' gene (part of ''pol'' gene in some viruses).
# dUTPase DU encoded by the ''pro'' gene (part of ''pol'' gene in some viruses), the role of which is still unknown. Protein size 14000 Da.
Gene regulatory proteins:
# Tat: main trans-activator
# Rev: important for synthesis of major viral proteins
Accessory proteins:
# Nef: negative factor
# Vpr
Vpr is a Human immunodeficiency virus gene and protein product. Vpr stands for "Viral Protein R". Vpr, a 96 amino acid 14-kDa protein, plays an important role in regulating nuclear import of the HIV-1 pre-integration complex, and is required for ...
: regulatory protein
# Vif: APOBEC3 inhibitor
# Vpu/ Vpx: unique to each type of HIV
# p6: part of gag
Antigenic properties
Serological relationships: Antigen
In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response.
...
determinants are type specific and group specific. Antigen determinants that possess type-specific reactivity are found on the envelope. Antigen determinants that possess type-specific reactivity and are involved in antibody mediated neutralization are found on the glycoproteins
Glycoproteins are proteins which contain oligosaccharide (sugar) chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known a ...
. Cross-reactivity has been found among some species of the same serotype, but not between members of different genera. Classification of members of this taxon
In biology, a taxon (back-formation from ''taxonomy''; : taxa) is a group of one or more populations of an organism or organisms seen by taxonomists to form a unit. Although neither is required, a taxon is usually known by a particular name and ...
is infrequently based on their antigenic properties.
Epidemiology
* Host range: the virus's hosts are found in the orders Primates
Primates is an order of mammals, which is further divided into the strepsirrhines, which include lemurs, galagos, and lorisids; and the haplorhines, which include tarsiers and simians ( monkeys and apes). Primates arose 74–63 ...
(humans, apes and monkeys), Carnivora
Carnivora ( ) is an order of placental mammals specialized primarily in eating flesh, whose members are formally referred to as carnivorans. The order Carnivora is the sixth largest order of mammals, comprising at least 279 species. Carnivor ...
(cats, dogs and other carnivores), Perissodactyla
Perissodactyla (, ), or odd-toed ungulates, is an order of ungulates. The order includes about 17 living species divided into three families: Equidae (horses, asses, and zebras), Rhinocerotidae (rhinoceroses), and Tapiridae (tapirs). They t ...
and Artiodactyla
Artiodactyls are placental mammals belonging to the order (biology), order Artiodactyla ( , ). Typically, they are ungulates which bear weight equally on two (an even number) of their five toes (the third and fourth, often in the form of a hoof ...
(single and double-toed hooved mammals).
* Transmission
Transmission or transmit may refer to:
Science and technology
* Power transmission
** Electric power transmission
** Transmission (mechanical device), technology that allows controlled application of power
*** Automatic transmission
*** Manual tra ...
: transmitted by means not involving a vector
Vector most often refers to:
* Euclidean vector, a quantity with a magnitude and a direction
* Disease vector, an agent that carries and transmits an infectious pathogen into another living organism
Vector may also refer to:
Mathematics a ...
.
* Geographic distribution: worldwide.
Physicochemical and physical properties
* General
** Buoyant
Buoyancy (), or upthrust, is the force exerted by a fluid opposing the weight of a partially or fully immersed object (which may be also be a parcel of fluid). In a column of fluid, pressure increases with depth as a result of the weight of t ...
density 1.16–1.18 g cm−3 in sucrose
Sucrose, a disaccharide, is a sugar composed of glucose and fructose subunits. It is produced naturally in plants and is the main constituent of white sugar. It has the molecular formula .
For human consumption, sucrose is extracted and refined ...
** Virions sensitive to heat, detergent
A detergent is a surfactant or a mixture of surfactants with Cleanliness, cleansing properties when in Concentration, dilute Solution (chemistry), solutions. There are a large variety of detergents. A common family is the alkylbenzene sulfonate ...
s, and formaldehyde
Formaldehyde ( , ) (systematic name methanal) is an organic compound with the chemical formula and structure , more precisely . The compound is a pungent, colourless gas that polymerises spontaneously into paraformaldehyde. It is stored as ...
** Infectivity not affected by UV irradiation
Classed as having ''class C'' morphology
Morphology, from the Greek and meaning "study of shape", may refer to:
Disciplines
*Morphology (archaeology), study of the shapes or forms of artifacts
*Morphology (astronomy), study of the shape of astronomical objects such as nebulae, galaxies, ...
* Nucleic acid
Nucleic acids are large biomolecules that are crucial in all cells and viruses. They are composed of nucleotides, which are the monomer components: a pentose, 5-carbon sugar, a phosphate group and a nitrogenous base. The two main classes of nuclei ...
** Virions contain 2% nucleic acid
Nucleic acids are large biomolecules that are crucial in all cells and viruses. They are composed of nucleotides, which are the monomer components: a pentose, 5-carbon sugar, a phosphate group and a nitrogenous base. The two main classes of nuclei ...
** Genome
A genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as ...
consists of a dimer
** Virions contain one molecule of (each) linear positive-sense single stranded RNA
Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself (non-coding RNA) or by forming a template for the production of proteins (messenger RNA). RNA and deoxyrib ...
.
** Total genome length is of one monomer
A monomer ( ; ''mono-'', "one" + '' -mer'', "part") is a molecule that can react together with other monomer molecules to form a larger polymer chain or two- or three-dimensional network in a process called polymerization.
Classification
Chemis ...
ranges from 8k-10k nt (depending on the virus).
** Genome sequence has terminal repeated sequences; long terminal repeat
A long terminal repeat (LTR) is a pair of identical sequences of DNA, several hundred base pairs long, which occur in eukaryotic genomes on either end of a series of genes or pseudogenes that form a retrotransposon or an endogenous retrovirus o ...
s (LTR) (of about 600 nt)
** The 5' end of the genome has a cap
** Cap sequence of type 1 m7G5ppp5'GmpNp
** 3' end of each monomer has a poly (A) tract.
** 2 copies packed per particle (held together by Watson-Crick baseparing to form a dimer).
* There are 11 proteins
** Virions contain 60% protein
** Five (major)structural virion proteins have been found so far
* Lipids
Lipids are a broad group of organic compounds which include fats, waxes, sterols, fat-soluble vitamins (such as vitamins Vitamin A, A, Vitamin D, D, Vitamin E, E and Vitamin K, K), monoglycerides, diglycerides, phospholipids, and others. The fu ...
: Virions contain 35% lipid
Lipids are a broad group of organic compounds which include fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include storing ...
.
* Carbohydrates
A carbohydrate () is a biomolecule composed of carbon (C), hydrogen (H), and oxygen (O) atoms. The typical hydrogen-to-oxygen atomic ratio is 2:1, analogous to that of water, and is represented by the empirical formula (where ''m'' and ''n'' ma ...
: Other compounds detected in the particles 3% carbohydrates.
Use as gene delivery vectors
Lentivirus is primarily a research tool used to introduce a gene product into in vitro
''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...
systems or animal models. Large-scale collaborative efforts are underway to use lentiviruses to block the expression of a specific gene using RNA interference
RNA interference (RNAi) is a biological process in which RNA molecules are involved in sequence-specific suppression of gene expression by double-stranded RNA, through translational or transcriptional repression. Historically, RNAi was known by ...
technology in high-throughput formats. Conversely, lentivirus are also used to stably over-express certain genes, thus allowing researchers to examine the effect of increased gene expression in a model system.
Another common application is to use a lentivirus to introduce a new gene into human or animal cells. For example, a model of mouse hemophilia
Haemophilia (British English), or hemophilia (American English) (), is a mostly inherited genetic disorder that impairs the body's ability to make blood clots, a process needed to stop bleeding. This results in people bleeding for a long ...
is corrected by expressing wild-type platelet-factor VIII
Coagulation factor VIII (Factor VIII, FVIII, also known as anti-hemophilic factor (AHF)) is an essential blood clotting protein. In humans, it is encoded by ''F8'' gene. Defects in this gene result in hemophilia A, an X-linked bleeding disorder ...
, the gene that is mutated in human hemophilia. Lentiviral infection has advantages over other gene-therapy methods including high-efficiency infection of dividing and non-dividing cells, long-term stable expression of a transgene
A transgene is a gene that has been transferred naturally, or by any of a number of genetic engineering techniques, from one organism to another. The introduction of a transgene, in a process known as transgenesis, has the potential to change the ...
, and low immunogenicity.
Lentiviruses have also been successfully used for transduction of diabetic mice with the gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
encoding PDGF
Platelet-derived growth factor (PDGF) is one among numerous growth factors that regulate cell growth and division. In particular, PDGF plays a significant role in blood vessel formation, the growth of blood vessels from already-existing blood ...
(platelet-derived growth factor), a therapy being considered for use in humans. Finally, lentiviruses have been also used to elicit an immune response against tumor antigens. These treatments, like most current gene therapy experiments, show promise but are yet to be established as safe and effective in controlled human studies.
Gammaretroviral and lentiviral vectors have so far been used in more than 300 clinical trials, addressing treatment options for various diseases.
See also
* Visna virus
Notes
References
*
*
*
Further reading
ICTV taxonomy of ''Lentivirus''
*
*
External links
{{Authority control
*
Virotherapy
Virus genera