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The human immunodeficiency viruses (HIV) are two species of ''
Lentivirus ''Lentivirus'' is a genus Genus (plural genera) is a taxonomic rank Taxonomy (general) is the practice and science of classification of things or concepts, including the principles that underlie such classification. The term may also refer ...

Lentivirus
'' (a subgroup of
retrovirus A retrovirus is a type of virus that inserts a 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 ...

retrovirus
) that infect humans. Over time, they cause
acquired immunodeficiency syndrome Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual may ...
(AIDS), a condition in which progressive failure of the
immune system The immune system is a network of biological processes that protects an organism In biology, an organism (from Ancient Greek, Greek: ὀργανισμός, ''organismos'') is any individual contiguous system that embodies the Life#Biolog ...
allows life-threatening
opportunistic infection An opportunistic infection is an infection An infection is the invasion of an organism's body Tissue (biology), tissues by Pathogen, disease-causing agents, their multiplication, and the reaction of host (biology), host tissues to the infectiou ...
s and
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumor A benign tumor is a mass of cells Cell most often refers to: * Cell (biolo ...

cancer
s to thrive. Without treatment, average survival time after infection with HIV is estimated to be 9 to 11 years, depending on the HIV subtype. In most cases, HIV is a
sexually transmitted infection Sexually transmitted infections (STIs), also referred to as sexually transmitted diseases (STDs) and the older term venereal disease, are s that are by , especially , and . STIs often do not initially cause symptoms, which results in a ris ...

sexually transmitted infection
and
occurs
occurs
by contact with or transfer of
blood Blood is a body fluid in humans and other animals that delivers necessary substances such as nutrients and oxygen to the Cell (biology), cells and transports metabolic waste products away from those same cells. In vertebrates, it is composed ...

blood
,
pre-ejaculate Pre-ejaculate (also known as pre-ejaculatory fluid, pre-seminal fluid or Cowper's fluid, and colloquially as ''pre-cum'') is a clear, colorless, viscous The viscosity of a fluid In physics, a fluid is a substance that continually Deforma ...

pre-ejaculate
,
semen Semen, also known as seminal fluid, is an organic fluid created to contain spermatozoon, spermatozoa. It is secreted by the gonads (sexual glands) and other sexual organs of male or hermaphrodite, hermaphroditic animals and can fertilization, f ...

semen
, and
vaginal fluids
vaginal fluids
. Research has shown (for both same-sex and opposite-sex couples) that HIV is untransmittable through condomless sexual intercourse if the HIV-positive partner has a consistently undetectable viral load. Non-sexual transmission can occur from an infected mother to her infant during
pregnancy Pregnancy, also known as gestation, is the time during which one or more offspring In biology, offspring are the young born of living organism, organisms, produced either by a single organism or, in the case of sexual reproduction, two orga ...

pregnancy
, during
childbirth Childbirth, also known as labour or delivery, is the ending of pregnancy where one or more babies leaves the uterus by passing through the vagina or by Caesarean section. In 2015, there were about 135 million births globally. About 15 million ...

childbirth
by exposure to her blood or vaginal fluid, and through
breast milk . Breast milk or mother's milk is milk Milk is a nutrient-rich liquid food produced by the mammary gland A mammary gland is an exocrine gland in humans and other mammals that produces milk to feed young offspring. Mammals get their nam ...
. Within these bodily fluids, HIV is present as both free
virus A virus is a that only inside the living of an . Viruses infect all , from animals and plants to s, including and . Since 's 1892 article describing a non-bacterial infecting tobacco plants and the discovery of the by in 1898, more ...

virus
particles and virus within infected
immune cells White blood cells (WBCs), also called leukocytes or leucocytes, are the cells of the immune system The immune system is a network of biological processes that protects an organism In biology, an organism (from Ancient Greek, Greek: ...
. HIV infects vital cells in the human immune system, such as
helper T cells The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the immune system, particularly in the adaptive immune system. As their name suggests, they "help" the activity of ...
(specifically
CD4 In molecular biology, CD4 (cluster of differentiation#REDIRECT Cluster of differentiation {{Redirect category shell, 1= {{R from other capitalisation ... 4) is a glycoprotein Glycoproteins are protein Proteins are large biomolecules ...
+ T cells),
macrophage Macrophages (abbreviated as Mφ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell White blood cells (WBCs), also called leukocytes or leucocytes, are the ...

macrophage
s, and
dendritic cell Dendritic cells (DCs) are antigen-presenting cells (also known as ''accessory cells'') of the mammal Mammals (from Latin language, Latin , 'breast') are a group of vertebrate animals constituting the class (biology), class Mammalia (), an ...

dendritic cell
s. HIV infection leads to low levels of CD4+ T cells through a number of mechanisms, including
pyroptosisPyroptosis is a highly inflammatory form of lytic programmed cell death that occurs most frequently upon infection with intracellular pathogens and is likely to form part of the antimicrobial response. This process promotes the rapid clearance of ...
of abortively infected T cells,
apoptosis Apoptosis (from Ancient Greek wikt:ἀπόπτωσις, ἀπόπτωσις, ''apóptōsis'', "falling off") is a form of programmed cell death that occurs in multicellular organisms. Biochemistry, Biochemical events lead to characteristic cell ...

apoptosis
of uninfected bystander cells, direct viral killing of infected cells, and killing of infected CD4+ T cells by CD8+ cytotoxic lymphocytes that recognize infected cells. When CD4+ T cell numbers decline below a critical level,
cell-mediated immunity Cell-mediated immunity is an immune response that does not involve antibodies. Rather, cell-mediated immunity is the activation of phagocytes, antigen-specific cytotoxic T-lymphocytes A T cell is a type of lymphocyte. T cells are one of the im ...
is lost, and the body becomes progressively more susceptible to opportunistic infections, leading to the development of AIDS.


Virology


Classification

HIV is a member of the
genus Genus /ˈdʒiː.nəs/ (plural genera /ˈdʒen.ər.ə/) is a taxonomic rank In biological classification In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure ...
''
Lentivirus ''Lentivirus'' is a genus Genus (plural genera) is a taxonomic rank Taxonomy (general) is the practice and science of classification of things or concepts, including the principles that underlie such classification. The term may also refer ...

Lentivirus
'', part of the family ''
Retroviridae A retrovirus is a type of virus A virus is a submicroscopic infectious agent that Viral replication, replicates only inside the living Cell (biology), cells of an organism. Viruses infect all types of life forms, from animals and plant ...
''. Lentiviruses have many morphologies and
biological Biology is the natural science Natural science is a branch of science Science (from the Latin word ''scientia'', meaning "knowledge") is a systematic enterprise that Scientific method, builds and Taxonomy (general), organizes knowl ...

biological
properties in common. Many species are infected by lentiviruses, which are characteristically responsible for long-duration illnesses with a long
incubation period Incubation period (also known as the latent period or latency period) is the time elapsed between exposure to a pathogenic In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical st ...
. Lentiviruses are transmitted as
single-stranded When referring to Transcription (genetics), DNA transcription, the coding strand is the DNA strand whose Nucleobase, base sequence is identical to the base sequence of the RNA transcript produced (although with thymine replaced by uracil). It is th ...
, positive-
sense A sense is a biological system A biological system is a complex biological network, network which connects several biologically relevant entities. Biological organization spans several scales and are determined based different structures dependi ...
, enveloped
RNA virus An RNA virus is a virus A virus is a submicroscopic infectious agent that Viral replication, replicates only inside the living Cell (biology), cells of an organism. Viruses infect all types of life forms, from animals and plants to micr ...
es. Upon entry into the target cell, the viral
RNA Ribonucleic acid (RNA) is a polymer A polymer (; Greek ''wikt:poly-, poly-'', "many" + ''wikt:-mer, -mer'', "part") is a Chemical substance, substance or material consisting of very large molecules, or macromolecules, composed of many Repe ...

RNA
genome In the fields of molecular biology and genetics, a genome is all genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The genome includes both the genes (the coding regions) and the noncodin ...

genome
is converted (reverse transcribed) into double-stranded
DNA Deoxyribonucleic acid (; DNA) is a molecule File:Pentacene on Ni(111) STM.jpg, A scanning tunneling microscopy image of pentacene molecules, which consist of linear chains of five carbon rings. A molecule is an electrically neutral gro ...

DNA
by a virally encoded enzyme,
reverse transcriptase A reverse transcriptase (RT) is an enzyme Enzymes () are s that act as s (biocatalysts). Catalysts accelerate . The molecules upon which enzymes may act are called , and the enzyme converts the substrates into different molecules known a ...
, that is transported along with the viral genome in the virus particle. The resulting viral DNA is then imported into the
cell nucleus In , the nucleus (pl. ''nuclei''; from or , meaning ''kernel'' or ''seed'') is a found in . Eukaryotes usually have a single nucleus, but a few cell types, such as mammalian s, have , and a few others including s have . The main structure ...

cell nucleus
and integrated into the cellular DNA by a virally encoded enzyme,
integrase Retroviral integrase (IN) is an enzyme Enzymes () are s that act as s (biocatalysts). Catalysts accelerate . The molecules upon which enzymes may act are called , and the enzyme converts the substrates into different molecules known as . ...
, and host co-factors. Once integrated, the virus may become latent, allowing the virus and its host cell to avoid detection by the immune system, for an indeterminate amount of time. The HIV virus can remain dormant in the human body for up to ten years after primary infection; during this period the virus does not cause symptoms. Alternatively, the integrated viral DNA may be transcribed, producing new RNA genomes and viral proteins, using host cell resources, that are packaged and released from the cell as new virus particles that will begin the replication cycle anew. Two types of HIV have been characterized: HIV-1 and HIV-2. HIV-1 is the virus that was initially discovered and termed both lymphadenopathy associated virus (LAV) and human T-lymphotropic virus 3 (HTLV-III). HIV-1 is more
virulent Virulence is a pathogen In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interactions, Physiology, ...
and more infective than HIV-2, and is the cause of the majority of HIV infections globally. The lower infectivity of HIV-2, compared to HIV-1, implies that fewer of those exposed to HIV-2 will be infected per exposure. Due to its relatively poor capacity for transmission, HIV-2 is largely confined to
West Africa West Africa or Western Africa is the westernmost region of . The defines Western Africa as the 17 countries of , , , , , , , , , , , , , , , and as well as .Paul R. Masson, Catherine Anne Pattillo, "Monetary union in West Africa (ECOWAS): is i ...

West Africa
.


Structure and genome

HIV is different in structure from other retroviruses. It is roughly spherical with a diameter of about 120  nm, around 60 times smaller than a
red blood cell Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek Greek may refer to: Greece Anything of, from ...

red blood cell
.Compared with overview in: It is composed of two copies of positive-
sense A sense is a biological system A biological system is a complex biological network, network which connects several biologically relevant entities. Biological organization spans several scales and are determined based different structures dependi ...
single-stranded When referring to Transcription (genetics), DNA transcription, the coding strand is the DNA strand whose Nucleobase, base sequence is identical to the base sequence of the RNA transcript produced (although with thymine replaced by uracil). It is th ...
RNA Ribonucleic acid (RNA) is a polymer A polymer (; Greek ''wikt:poly-, poly-'', "many" + ''wikt:-mer, -mer'', "part") is a Chemical substance, substance or material consisting of very large molecules, or macromolecules, composed of many Repe ...

RNA
that codes for the virus's nine
gene In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interactions, Physiology, physiological mecha ...

gene
s enclosed by a conical
capsid A capsid is the protein shell of a , enclosing its . It consists of several ic (repeating) structural subunits made of called s. The observable 3-dimensional morphological subunits, which may or may not correspond to individual proteins, are ca ...
composed of 2,000 copies of the viral protein p24. The single-stranded RNA is tightly bound to nucleocapsid proteins, p7, and enzymes needed for the development of the virion such as
reverse transcriptase A reverse transcriptase (RT) is an enzyme Enzymes () are s that act as s (biocatalysts). Catalysts accelerate . The molecules upon which enzymes may act are called , and the enzyme converts the substrates into different molecules known a ...
,
protease A protease (also called a peptidase or proteinase) is an enzyme Enzymes () are s that act as s (biocatalysts). Catalysts accelerate . The molecules upon which enzymes may act are called , and the enzyme converts the substrates into differe ...

protease
s,
ribonuclease Ribonuclease (commonly abbreviated RNase) is a type of nuclease that catalyzes the degradation of RNA into smaller components. Ribonucleases can be divided into endoribonucleases and exoribonucleases, and comprise several sub-classes within t ...
and
integrase Retroviral integrase (IN) is an enzyme Enzymes () are s that act as s (biocatalysts). Catalysts accelerate . The molecules upon which enzymes may act are called , and the enzyme converts the substrates into different molecules known as . ...
. A matrix composed of the viral protein p17 surrounds the capsid ensuring the integrity of the virion particle. This is, in turn, surrounded by the
viral envelope 250px, Schematic of a Cytomegalovirus, coat = envelope A viral envelope is the outermost layer of many types of virus A virus is a submicroscopic infectious agent that Viral replication, replicates only inside the living Cell (biology), ...
, that is composed of the
lipid bilayer The lipid bilayer (or phospholipid bilayer) is a thin polar membrane A polarized membrane is a lipid bilayer, lipid membrane that has a positive electrical charge on one side and a negative charge on another side, which produces the resting pote ...
taken from the membrane of a human host cell when the newly formed virus particle buds from the cell. The viral envelope contains proteins from the host cell and relatively few copies of the HIV envelope protein, which consists of a cap made of three molecules known as glycoprotein (gp) 120, and a stem consisting of three
gp41 Gp41 also known as glycoprotein 41 is a subunit of the envelope protein complex is a protein complex functioning as a molecular biological machine A molecular machine, nanite, or nanomachine is a molecular component that produces quasi-mechani ...
molecules that anchor the structure into the viral envelope. The envelope protein, encoded by the HIV ''env'' gene, allows the virus to attach to target cells and fuse the viral envelope with the target
cell's membrane cell membrane vs. Prokaryotes The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates the cytoplasm, interior of all Cell (biolog ...

cell's membrane
releasing the viral contents into the cell and initiating the infectious cycle. As the sole viral protein on the surface of the virus, the envelope protein is a major target for
HIV vaccine A HIV vaccine is a potential vaccine that could be either a preventive vaccine or a therapeutic vaccine, which means it would either protect individuals from being infected with HIV or treat HIV-infected individuals. It is thought that a HIV va ...
efforts. Over half of the mass of the trimeric envelope spike is N-linked
glycan The terms glycan and polysaccharide , a beta-glucan is an example of a (1→4)-β-D-glucan composed of glucose Glucose is a simple sugar with the Chemical formula#Molecular formula, molecular formula . Glucose is the most abundant monosaccharid ...

glycan
s. The density is high as the glycans shield the underlying viral protein from neutralisation by antibodies. This is one of the most densely glycosylated molecules known and the density is sufficiently high to prevent the normal maturation process of glycans during biogenesis in the endoplasmic and Golgi apparatus. The majority of the glycans are therefore stalled as immature 'high-mannose' glycans not normally present on human glycoproteins that are secreted or present on a cell surface. The unusual processing and high density means that almost all broadly neutralising antibodies that have so far been identified (from a subset of patients that have been infected for many months to years) bind to, or are adapted to cope with, these envelope glycans. The molecular structure of the viral spike has now been determined by
X-ray crystallography X-ray crystallography (XRC) is the experimental science determining the atomic and molecular structure of a crystal A crystal or crystalline solid is a solid material whose constituents (such as atoms, molecules, or ions) are arranged in a ...

X-ray crystallography
and
cryogenic electron microscopy Cryo-TEM image of GroEL suspended in amorphous ice">GroEL.html" ;"title="Cryo-TEM image of GroEL">Cryo-TEM image of GroEL suspended in amorphous ice at × magnification Cryogenic electron microscopy (cryo-EM) is an electron microscopy An el ...
. These advances in structural biology were made possible due to the development of stable
recombinantRecombinant may refer to: * Recombinant organism A genetically modified organism (GMO) is any organism whose genetic material has been altered using genetic engineering techniques. The exact definition of a genetically modified organism and wha ...
forms of the viral spike by the introduction of an intersubunit disulphide bond and an
isoleucine Isoleucine (symbol Ile or I) is an α-amino acid Amino acids are organic compound , CH4; is among the simplest organic compounds. In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen chemical bon ...

isoleucine
to
proline Proline (symbol Pro or P) is an organic acid classed as a proteinogenic amino acid Proteinogenic amino acids are amino acids that are incorporated biosynthetically into proteins during translation (biology), translation. The word "proteinogenic ...

proline
mutation In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interactions, Physiology, physiological mechan ...
( radical replacement of an amino acid) in gp41. The so-called SOSIP trimers not only reproduce the antigenic properties of the native viral spike, but also display the same degree of immature glycans as presented on the native virus. Recombinant trimeric viral spikes are promising vaccine candidates as they display less non-neutralising
epitopeAn epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibody, antibodies, B cells, or T cells. The epitope is the specific piece of the antigen to which an antibody binds ...

epitope
s than recombinant monomeric gp120, which act to suppress the immune response to target epitopes. The RNA genome consists of at least seven structural landmarks ( LTR,
TAR Tar is a dark brown or black viscous The viscosity of a fluid In physics, a fluid is a substance that continually Deformation (mechanics), deforms (flows) under an applied shear stress, or external force. Fluids are a Phase (matter), ...
, RRE, PE, SLIP, CRS, and INS), and nine genes (''gag'', ''pol'', and ''env'', ''tat'', ''rev'', ''nef'', ''vif'', ''vpr'', ''vpu'', and sometimes a tenth ''tev'', which is a fusion of ''tat'', ''env'' and ''rev''), encoding 19 proteins. Three of these genes, ''gag'', ''pol'', and ''env'', contain information needed to make the structural proteins for new virus particles. For example, ''env'' codes for a protein called gp160 that is cut in two by a cellular protease to form gp120 and gp41. The six remaining genes, ''tat'', ''rev'', ''nef'', ''vif'', ''vpr'', and ''vpu'' (or ''vpx'' in the case of HIV-2), are regulatory genes for proteins that control the ability of HIV to infect cells, produce new copies of virus (replicate), or cause disease. The two '' tat'' proteins (p16 and p14) are transcriptional transactivators for the LTR promoter acting by binding the TAR RNA element. The TAR may also be processed into
microRNA A microRNA (abbreviated miRNA) is a small single-stranded non-coding RNA A non-coding RNA (ncRNA) is an RNA Ribonucleic acid (RNA) is a polymer A polymer (; Greek '' poly-'', "many" + '' -mer'', "part") is a substance or materi ...
s that regulate the
apoptosis Apoptosis (from Ancient Greek wikt:ἀπόπτωσις, ἀπόπτωσις, ''apóptōsis'', "falling off") is a form of programmed cell death that occurs in multicellular organisms. Biochemistry, Biochemical events lead to characteristic cell ...

apoptosis
genes ''
ERCC1 DNA excision repair protein ERCC-1 is a protein that in humans is encoded by the ''ERCC1'' gene. Together with ERCC4, ERCC1 forms the ERCC1-XPF enzyme complex that participates in DNA repair and Genetic recombination, DNA recombination. Many aspec ...
'' and ''
IER3 Radiation-inducible immediate-early gene IEX-1 is a protein Proteins are large biomolecule , showing alpha helices, represented by ribbons. This poten was the first to have its suckture solved by X-ray crystallography by Max Perutz and S ...
''. The ''rev'' protein (p19) is involved in shuttling RNAs from the nucleus and the cytoplasm by binding to the RRE RNA element. The ''vif'' protein (p23) prevents the action of
APOBEC3G APOBEC3G (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3G) is a human enzyme encoded by the ''APOBEC3G'' gene that belongs to the APOBEC superfamily of proteins. This family of proteins has been suggested to play an important r ...
(a cellular protein that deaminates
cytidine Cytidine (symbol A symbol is a mark, sign, or that indicates, signifies, or is understood as representing an , , or . Symbols allow people to go beyond what is n or seen by creating linkages between otherwise very different s and s. All ( ...

cytidine
to
uridine Uridine (symbol A symbol is a mark, sign, or word In linguistics, a word of a spoken language can be defined as the smallest sequence of phonemes that can be uttered in isolation with semantic, objective or pragmatics, practical meani ...
in the single-stranded viral DNA and/or interferes with reverse transcription). The ''
vpr Vpr is a HIV, 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 ...
'' protein (p14) arrests
cell division Cell division is the process by which a parent cell (biology), cell divides into two or more daughter cells. Cell division usually occurs as part of a larger cell cycle. In eukaryotes, there are two distinct types of cell division; a vegetative ...

cell division
at G2/M. The ''nef'' protein (p27) down-regulates
CD4 In molecular biology, CD4 (cluster of differentiation#REDIRECT Cluster of differentiation {{Redirect category shell, 1= {{R from other capitalisation ... 4) is a glycoprotein Glycoproteins are protein Proteins are large biomolecules ...
(the major viral receptor), as well as the
MHC class I MHC class I molecules are one of two primary classes of major histocompatibility complex The major histocompatibility complex (MHC) is a large locus on vertebrate DNA containing a set of closely linked polymorphic genes that code for cell su ...
and class II molecules. ''Nef'' also interacts with
SH3 domain The SRC Homology 3 Domain (or SH3 domain) is a small protein domain A protein domain is a region of the protein's Peptide, polypeptide chain that is self-stabilizing and that folds independently from the rest. Each domain forms a compact pr ...
s. The ''vpu'' protein (p16) influences the release of new virus particles from infected cells. The ends of each strand of HIV RNA contain an RNA sequence called a
long terminal repeat A long terminal repeat (LTR) is a pair of identical sequences of DNA Deoxyribonucleic acid (; DNA) is a molecule File:Pentacene on Ni(111) STM.jpg, A scanning tunneling microscopy image of pentacene molecules, which consist of linear ch ...
(LTR). Regions in the LTR act as switches to control production of new viruses and can be triggered by proteins from either HIV or the host cell. The Psi element is involved in viral genome packaging and recognized by ''gag'' and ''rev'' proteins. The SLIP element () is involved in the
frameshift Ribosomal frameshifting, also known as translational frameshifting or translational recoding, is a biological phenomenon that occurs during Translation (biology), translation that results in the production of multiple, unique proteins from a single ...
in the ''gag''-''pol''
reading frame In molecular biology Molecular biology is the branch of biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, mol ...

reading frame
required to make functional ''pol''.


Tropism

The term
viral tropism{{one source, article, date=March 2013 Tissue tropism is the cells and tissues of a host (biology), host that support growth of a particular virus (biology), virus or bacteria, bacterium. Some bacteria and viruses have a broad tissue tropism and can ...
refers to the cell types a virus infects. HIV can infect a variety of immune cells such as CD4+ T cells,
macrophage Macrophages (abbreviated as Mφ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell White blood cells (WBCs), also called leukocytes or leucocytes, are the ...

macrophage
s, and microglial cells. HIV-1 entry to macrophages and CD4+ T cells is mediated through interaction of the virion envelope glycoproteins (gp120) with the CD4 molecule on the target cells' membrane and also with
chemokine Chemokines (), or chemotactic cytokines, are a family of small cytokine Cytokines are a broad and loose category of small protein Proteins are large biomolecule , showing alpha helices, represented by ribbons. This poten was the firs ...
co-receptor A co-receptor is a cell surface receptor that binds a signalling molecule in addition to a primary receptor in order to facilitate Ligand (biochemistry), ligand recognition and initiate biological processes, such as entry of a pathogen into a host c ...
s. Macrophage-tropic (M-tropic) strains of HIV-1, or non- syncytia-inducing strains (NSI; now called R5 viruses) use the ''β''-chemokine receptor,
CCR5 C-C chemokine receptor type 5, also known as CCR5 or CD195, is a protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array o ...
, for entry and are thus able to replicate in both macrophages and CD4+ T cells. This CCR5 co-receptor is used by almost all primary HIV-1 isolates regardless of viral genetic subtype. Indeed, macrophages play a key role in several critical aspects of HIV infection. They appear to be the first cells infected by HIV and perhaps the source of HIV production when CD4+ cells become depleted in the patient. Macrophages and microglial cells are the cells infected by HIV in the
central nervous system The central nervous system (CNS) is the part of the nervous system In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecu ...

central nervous system
. In the
tonsil The tonsils are a set of lymphoid organs facing into the aerodigestive tract {{Short pages monitor * {{DEFAULTSORT:Hiv HIV/AIDS, * Causes of death Discovery and invention controversies IARC Group 2B carcinogens Lentiviruses Sexually transmitted diseases and infections 1983 in biology