Amino acid |
|
The chemical building blocks from
which proteins are made. Instructions for the production of amino acids are coded in DNA (or in some viruses, RNA), and
the sequence of codes along a length of DNA (or RNA) determines which protein is made. |
|
|
|
Amplicon |
|
A PCR product that is a copy of
the original DNA or RNA target region. |
|
|
|
Amplification |
|
The process of producing many DNA
copies from one original DNA or RNA target region. PCR is a nucleic acid amplification
technique. |
|
|
|
Anneal |
|
The biochemical process of
hybridising, or binding, two segments of complementary nucleic acid (RNA or DNA) at an
optimal temperature of 40-65�C. |
|
|
|
Antimicrobial |
|
A drug that inhibits or kills a
microorganism (e.g., virus, bacteria or fungus). |
|
|
|
Bacterium
|
|
A one-celled organism, smaller
than a human cell, whose genetic material is not confined within a nucleus. |
|
|
|
Bases |
|
The components of DNA which pair
to make the rungs of the DNA ladder. There are four types of bases in DNA
which bond in complementary pairs: Adenine to Thymine and Cytosine to Guanine. In RNA, the
base Uracil replaces Thymine. |
|
|
|
Baseline
Measurement |
|
A baseline viral load measurement
is calculated from two tests performed one to two weeks apart. |
|
|
|
Buffer |
|
A general term used when
referring to a solution or reagent that can resist a change in pH upon the addition of
either acidic or alkaline material. |
|
|
|
CD4 cell count |
|
HIV
attaches itself to an antigen, CD4, on the surface of certain lymphocytes (CD4 cells),
which have an important role in the bodys immune system. Cells infected with HIV are
destroyed by other lymphocytes (see cytotoxicity) so
the CD4 cell count is low in untreated PWA's infected with HIV. In PWA's on antiviral
therapy the CD4 cell count shows how effective treatment is in destroying the virus. |
|
|
|
cDNA |
|
Complementary DNA. The product of
reverse transcription of RNA. |
|
Combination
therapy |
|
Treatment with more than one drug
simultaneously. In HIV combination therapy is more effective than monotherapy
in preventing the development of drug resistance. |
|
Co-receptor |
|
A receptor that acts together with another
receptor. |
|
|
|
Cross-resistance |
|
Resistance
of a virus to more than one drug of the same group: e.g.
resistance to certain protease inhibitors may result in a PWA being unable to benefit from
other protease inhibitors. |
|
|
|
Cytoplasm
|
|
Cell contents other than the nucleus. |
|
|
|
Cytotoxicity |
|
Cell killing. Some lymphocytes are cytotoxic, and their function is to destroy
cells infected with a pathogen such as HIV. |
|
|
|
Denature |
|
The process of separating double
stranded DNA into single strands by breaking the hydrogen bonds between bases. This is
most often accomplished by heating the DNA solution to temperatures greater than 90�C or
by treating it with strong alkali. |
|
|
|
DNA |
|
Deoxyribonucleic acid. A long
molecule that in most organisms carries the genetic information in the form of a code.
(See Gene). |
|
|
|
DNA Polymerase |
|
An enzyme that can synthesize new
complementary DNA strands using a DNA template and primer. Several of these enzymes are
commercially available, including Taq DNA Polymerase and rTth DNA
Polymerase. |
|
|
|
Double helix |
|
Refers to the structure of DNA which consists
of two antiparallel polynucleotide chains held together by hydrogen bonds. They are
twisted around each other in a helical formation. |
|
|
|
Enzyme |
|
A protein that initiates and
controls a chemical reaction in the body or in a cell without itself becoming changed
during the reaction. |
|
|
|
Extension |
|
Refers to the elongation of the DNA chain that
is being synthesized using the parent DNA strand as the template for synthesis of that
daughter strand. This is a natural process that occurs during DNA replication. Extension
occurs during the PCR process with DNA Polymerases (Taq or rTth). |
|
|
|
Fitness |
|
The advantage that a particular
strain of an organism has over other strains in the same population. The fittest strain of
HIV, e.g. a drug-resistant one in an environment in which drug
is present, will replicate faster than less fit strains and become the dominant one. |
|
|
|
Gene |
|
The basic unit of inheritance,
consisting of DNA or (in some viruses
such as HIV) RNA. Carries coded
instructions for cells to produce proteins essential to life. |
|
|
|
Genetic barrier |
|
The need for multiple mutations to make a virus
resistant to the various drugs used in combination therapy. |
|
|
|
Genotype |
|
The total genetic make-up of an
organism (e.g. virus or human). The HIV genotype can include
genes that make the virus resistant to drug treatments. |
|
|
|
Half-life |
|
The time taken for the amount of
drug in the body (or its concentration in plasma) to be reduced by 50% as a result of
metabolism and excretion. |
|
|
|
HIV |
|
Human immunodeficiency virus. In an untreated infected person suppresses the immune
system, leading to severe infections and AIDS. |
|
|
|
Host |
|
An organism (e.g. human) in which
another organism (e.g. HIV) lives and reproduces. |
|
|
|
Integrase |
|
A viral enzyme that integrates
the viral genetic code into the host cells DNA. |
|
|
|
Intracellular |
|
Inside the cell. |
|
|
|
Intercellular |
|
Outside the cell. |
|
|
|
Logs |
|
Short for logarithm. The number
of times ten must be multiplied with itself to equal a number. For example, 100,000 is 5
logs (10 x 10 x 10 x 10 x 10). Logs are used to express viral load results and changes in
viral load. |
|
|
|
Lymphocyte |
|
White blood cells. |
|
|
|
Master Mix |
|
Chemical solution which contains
everything needed for reagent PCR. This solution includes nucleotides, enzyme
cofactors, Taq or rTth DNA Polymerase, AmpErase�,
buffers and primers. |
|
|
|
Membrane |
|
A thin pliable covering or
lining. The plasma membrane that surrounds an animal cells consists of a double layer of
fat (lipid) molecules, which protects the cell contents from the external environment. The
viral membrane that surrounds a virus is part of the host
plasma membrane. The virus sheds this membrane when it enters a new host cell, and
collects a new membrane as it leaves the host to infect other cells. |
|
|
|
Monotherapy |
|
Treatment with a single drug.
(See also Combination therapy). |
|
|
|
Mutant |
|
A gene,
cell or organism in which a mutation has occurred. |
|
|
|
Mutation |
|
A sudden change in a gene. In HIV some mutations make the
virus resistant to one or more antiviral drugs. |
|
|
|
Nadir |
|
See viralogical
nadir. |
|
|
|
Nucleotide |
|
A sub-unit of DNA or RNA, consisting of a base
(purine or pyrimidine), a sugar and a phosphate. The sequence of bases in adjacent
nucleotides within a gene determines which protein is encoded
by the gene. |
|
|
|
Nucleus
|
|
A discrete part of the cell
containing the genes and separated from the surrounding cytoplasm by a membrane. |
|
|
|
PCR |
|
Polymerase Chain Reaction. The process of
target amplification used in the AMPLICOR� Microwell Plate Tests and COBAS
AMPLICOR Analyser Automated PCR Tests. |
|
|
|
Phenotype |
|
The outward appearance or
behaviour of an organism (e.g. virus or human). The
phenotype depends partly on the organisms genotype and
partly on the environment (e.g. nutrients, temperature). Drug resistance in HIV is the
phenotypic expression of resistance genes. |
|
|
|
Pol gene |
|
A gene
found in HIV and other retroviruses.
It encodes reverse transcriptase and other essential enzymes
essential to retroviral replication inside the host
cell. Several pol mutations are known to be
associated with resistance to different antiviral
drugs. |
|
|
|
Polymerase |
|
An enzyme that is capable of
synthesizing new strands of DNA from a single stranded template and free deoxynucleotides
under appropriate reaction conditions. During PCR, Roche systems use Taq DNA
Polymerase to make DNA amplicon using the DNA strand as a template. rTth DNA
Polymerase is used to perform reverse transcription (synthesizing cDNA from RNA) and which
then, through PCR, produces DNA amplicon. |
|
|
|
Polymerase chain reaction |
|
A method that increases the
sensitivity of DNA testing (e.g. to detect HIV) by making multiple copies of the DNA sequence in question. |
|
|
|
Primers |
|
A small synthetic segment of DNA
used to initiate or "prime" the new DNA synthesis. In PCR, primers are small
segments of DNA of a defined length and sequence that are used to initiate DNA synthesis
by DNA Polymerase (Taq or rTth). |
|
|
|
Probe |
|
A small piece of DNA that is used
to isolate or detect complementary target in the reaction mixture. |
|
|
|
Protease |
|
An enzyme that breaks up proteins. |
|
|
|
Protein |
|
A molecule consisting of a chain
of amino acids. A major source of the building materials for
tissues (e.g. muscle, blood), enzymes, receptors and many other body components. |
|
|
|
Purines |
|
The name that classifies the
bases with a 2 ring structure, Adenine and Guanine. Purine bases will only bond with
pyrimidine bases. |
|
|
|
Pyrimidines |
|
The name that classifies the
bases with 1 ring structures: Thymine, Cytosine and Uracil. Pyrimidine bases will only
bond with purine bases. |
|
|
|
Receptor |
|
A protein
located on or in a cell, which recognises and binds to a specific type of molecule. |
|
|
|
Replication |
|
Viral reproduction. Viruses do not reproduce sexually; instead they multiply inside
the host cell by budding, making perhaps millions of copies of themselves each day in the lymphocytes of an infected person. |
|
|
|
Resistance |
|
The ability of a virus to resist the effects of antiviral drugs intended to stop
its replication. |
|
|
|
Retrovirus
|
|
A virus
whose genes are carried as RNA
and which converts RNA to DNA to enable it to integrate with
the host cell DNA. |
|
|
|
Reverse |
|
The process of making cDNA (complementary DNA)
transcription using an RNA template. An essential step in PCR for retroviruses, eg
HIV. |
|
|
|
Reverse
transcriptase |
|
A retrovirus
enzyme that synthesises DNA from RNA. |
|
|
|
Reverse transcription |
|
Synthesis of DNA from RNA. Occurs naturally in retroviruses. In other organisms RNA is synthesised from
DNA. |
|
|
|
RNA |
|
Ribonucleic acid. In most
organisms, the molecule that 'translates' the information coded by DNA
into proteins. In some viruses, such as HIV, the codes (genes) themselves
are carried in RNA. |
|
|
|
rTth DNA
Polymerase |
|
Recombinant thermostable DNA Polymerase
originally isolated from the bacterium Thermus thermophilus. rTth has
optimal activity at 70-80�C and survives the denaturation steps of PCR. In addition to
DNA Polymerase activity, it has efficient reverse transcriptase activity in the presence
of manganese. |
|
|
|
Selective pressure |
|
An environmental force (e.g. for HIV the presence of an antiviral drug) that allows a strain with
a certain gene (e.g. a resistance
mutation) to survive and multiply at the expense of other
strains. |
|
|
|
Sensitivity |
|
The susceptibility of an organism
(e.g. HIV) to inactivation or death by a drug. |
|
|
|
Strain |
|
A variety of organism defined by
the genes it contains. A population of an organism may
consist of several different strains. |
|
|
|
Taq DNA
Polymerase |
|
Thermostable DNA Polymerase
originally isolated from the bacterium Thermus aquaticus. Taq has optimal
activity at 70-80�C and is not degraded during the high heat denaturation steps of PCR. |
|
|
|
Target Sequence |
|
A nucleotide sequence of DNA or
RNA within the organism genome that is known, conserved and characteristic for the
intended test. |
|
Template |
|
An RNA
or DNA strand that provides the pattern for synthesis of a
complementary strand. In most organisms DNA is the template for RNA; in HIV and other retroviruses RNA
is the template for DNA. |
|
|
|
Thermal Cycler |
|
A programmable temperature block
that rapidly changes the temperatures among those needed to accomplish the Polymerase
Chain Reaction (PCR). A typical PCR method may have to cycle at 94�C then 55�C and then
72�C and repeat this cycle for as many as 30 to 40 cycles. This process is automated by
the COBAS AMPLICOR Analyser. |
|
|
|
T lymphocyte |
|
A white blood cell that
recognises foreign proteins (e.g., bacteria, transplanted
tissue) and mobilises other cells to destroy the invading organism or foreign tissue. HIV infects certain T lymphocytes (CD4 lymphocytes), thereby
causing immunodeficiency. |
|
|
|
Transcription |
|
The process of making RNA from
DNA. |
|
|
|
Viral load |
|
The number of copies of viral RNA per ml of plasma. An undetectable (i.e. very low) viral load
appears to be associated with a more durable response to treatment and is thus an aim of
antiviral therapy. |
|
|
|
Virological
nadir |
|
Point a which an
individuals viral load is at its lowest, as established by sequential viral load
testing. |
|
|
|
Virus |
|
A minute parasitic organism, much
smaller than a bacterium, which can replicate only
inside the cells of its host. Consists of a core of DNA or RNA surrounded by a protein coat.
Viral genes are integrated into the host's genes and instruct
the host cell to make viral protein. |
|
|
|
Wild type |
|
The natural (non-mutant) form of
a gene. |