primate genetic test data sheet
TRIM5α genotyping for
macaques
Test codes: GP006 - detection of Mamu-6
allele by PCR GP007 - detection of Mamu-7 allele by
PCR
The TRIM5α gene has
recently been identified as an important factor in restriction
of infectivity of immunodeficiency viruses. Homologs of this
gene have been identified in humans, nonhuman primates and some
other vertebrates.
The functional effect of
the TRIM5α protein appears to be somewhat species-specific. For
example, TRIM5α restricts SIV infection in Old World monkeys but
the human TRIM5α protein does not have a similar restrictive
function relative to HIV infection in humans.
The TRIM5α protein
possesses a characteristic tripartite structure, its three
structural motifs being ring, B Box 2, and coiled coil domains.
Together with other members of the TRIM family, TRIM5α also has
a C-terminal PRY/SPRY, or B30.2 domain, which is the most
important domain conferring antiviral specificity.
Several variants of the
TRIM5α protein have been described; they are named Mamu-1
through Mamu-7. In vitro
studies have shown that
Mamu-1, -2,
-3,
-4, and -5 can efficiently
restrict HIV-1 and MLV-N (N-tropic murine leukemia virus),
whereas Mamu-6
does not restrict either retrovirus (Newman et al. 2006).
The Mamu-7 variant, also
called TRIMCyp, has recently been discovered in New World owl
monkeys and in rhesus macaques. The Mamu-7 variant is created by
insertion of a cyclophilin A (CypA) cDNA by retrotransposition
into the seventh intron of the TRIM5α gene, leading to
replacement of the exon eight-encoded PRY/SPRY/B30.2 domain with
the cyclophilin A gene. This change alters antiviral specificity
and leads to restriction of retroviruses that recruit CypA to
their incoming capsid, including HIV-1, feline immunodeficiency
virus and simian immunodeficiency virus from Tantalus monkey
(SIVtan).
Characterization of the underlying genotype of the TRIM5α gene
is important for the proper selection of macaques for AIDS
studies.
Utilities:
-
Help confirm
TRIM5α
genotype in macaques
-
Prequalification of rhesus and cynomolgus
macaques for preclinical trials
References: Newman, R. M., Hall, L.,
Connole, M., Chen, G-L., Sato, S., Yuste, E., Diehl, W., Hunter,
E., Kaur, A., Miller, G.M. and Johnson, W.E. (2006) Balancing
selection and the evolution of functional polymorphism in Old
World monkey TRIM5α. PNAS 103: 19134-19139.
Specimen requirement:
0.2 ml whole blood in EDTA (purple top) tube, or buccal swab, or 0.2 ml fresh
or frozen tissue.
Contact Zoologix if advice is needed to determine an appropriate specimen type for a specific diagnostic application. For specimen types not listed here, please contact Zoologix to confirm specimen acceptability and shipping instructions.
For all specimen types, if
there will be a delay in shipping, or during very warm weather,
refrigerate specimens until shipped and ship with a cold pack
unless more stringent shipping requirements are specified.
Frozen specimens should be shipped so as to remain frozen in
transit. See
shipping instructions for more information.
Normal range:
Homozygous or heterozygous for the variant
Turnaround time: 3 business days
Methodology: PCR
|