Biomedical Engineering Reference
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animals of defined major histocompatibility complex
(MHC) it may also be important to include MHC type as
a criterion for selection of the founding cohort ( Baskin
et al., 1997 ). With continued refinement of the rhesus
macaque model for disease research, increasing demands
for animals of known genetic and disease background will
be inevitable.
that sexual or parenteral routes of infection are responsible
for the spread within colonies ( Ishikawa et al., 1987 ). The
highly cell-associated nature of STLV implies that it should
be relatively easy to eradicate from colonies. Commercial
ELISA assays for HTLV are available and due to cross-
reactivity can be used for serological screening for STLV in
colonies ( Meertens et al., 2001 ). If seropositive animals are
identified, samples should be sent to a commercial labo-
ratory for confirmational testing using Western blot assays.
Target Viruses for SPF Macaque Colonies
Macacine Herpes Virus (BV)
BV is a member of the alpha herpesvirus family and is
a common infection among all species of macaques in
which infection is normally self-limiting ( Weigler, 1992 ).
After BV infection of a macaque, the virus becomes latent
in sensory ganglia, and reactivation can occur during
periods of immunosuppression or stress ( Chellman et al.,
1992; Weigler et al., 1995 ). This virus is shed in secretions
such as saliva and is readily transmitted, with most animals
becoming seropositive by 2 years of age ( Weigler et al.,
1990, 1993 ). Of the viruses targeted for elimination in SPF
colonies, BV has proved most problematical ( Ward et al.,
2000; Ward and Hilliard, 2002 ). Various reports have
documented a phenomenon of delayed seroconversion, in
which an animal that has repeatedly tested BV seronegative
unexpectedly develops antibodies ( Ward and Hilliard,
1994 ). The occurrence of delayed BV seroconversion can
jeopardize the integrity of SPF colonies many years after
they have been founded. Although the mechanism
responsible for this phenomenon is not well understood, it
is hypothesized to occur when animals are infected at
a very early age and then a latent viral state is established
before an adequate antibody response is developed.
Simian Retrovirus Type D (SRV-D)
This is a group of closely related retroviruses that have been
isolated from most species of macaques ( Daniel et al.,
1984 ; Lerche et al., 1994; Marx et al., 1984 ). To date, seven
SRV-D serotypes have been recognized, and it has also
been shown that marked genetic variation exists among
individual isolates ( Marx et al., 1984; Marracci et al.,
1995 ). SRV-D exhibits broad cellular tropism, including
cells of lymphoid and nonlymphoid lineages ( Lackner
et al., 1988 ). This expansive tropism increases the potential
for spread of SRV-D between animals, as the virus can be
secreted in many bodily fluids ( Lerche, 1992; Gardner
et al., 2000 ). Transmission can occur both horizontally and
vertically, adding to the complexity of eliminating this
virus from nonhuman primate colonies ( Tsai et al., 1987;
Lerche et al., 1994 ). Another confounding problem with
eradicating SRV-D is the existence of animals that are virus
positive but antibody negative ( Wilkinson et al., 2003 ).
This state normally arises when infection has occurred in
utero or shortly after birth. To eliminate SRV-D from
a colony, it is important to incorporate serological assays to
screen for antibodies with PCR and virus isolation tech-
niques to detect the cohort of antibody-negative/virus-
positive animals. Cross-reactivity of antibodies between
different serotypes is directed mainly at the major capsid
protein p27 and transmembrane glycoprotein gp20 e 22.
These conserved regions are commonly used in serological
assays to test for SRV-D ( Kuller et al., 2005; Khan et al.,
2006 ). Viral isolation techniques involve culturing of
peripheral blood mononuclear cells (PBMCs) with
permissive cell lines such as Raji cells. If the animal is
SRV-D positive, syncytial cell formation will normally be
seen in approximately 3 weeks. Should syncytial cell
formation occur, microscopic examination of the culture or
PCR analysis should be performed. When PCR results are
positive, the isolate should be sequenced to confirm that it
is SRV-D rather than a closely related endogenous retro-
virus ( Morton et al., 2008 ).
Simian T Lymphotropic Virus (STLV)
This group of type C retroviruses is closely related to
human T lymphotropic virus types I and II ( Miyoshi et al.,
1983 ). Although STLV appears to have minimal health
consequences in immunocompetent macaques, it has been
linked to lymphoproliferative disorders in AIDS ( Homma
et al., 1984 ). STLV has a low zoonotic potential and
therefore has limited occupational health and safety risks;
however, infection of macaques has been shown to alter
cytokine profiles and thus could have a confounding effect
on immunological studies, particularly those involving
simian AIDs ( Lazo and Bailer, 1996; Carvalho et al., 2001 ).
For this reason, STLV has been targeted for elimination
from SPF programs. The incidence of STLV infection
within colonies varies dramatically, with reports of 0 e 20%
of animals being infected ( Daniel et al., 1988; Lerche et al.,
1994; Schillaci et al., 2005 ). The virus is highly cell asso-
ciated with primary tropism for CD4
Simian Immunodeficiency Virus (SIV)
SIV is known to infect various African species of
nonhuman primates, in which the virus causes minimal
clinical disease. However, infection of Asian species of
lymphocytes ( Gabet
et al., 2003 ). Transmission involves transfer of infected
lymphocytes from one animal to another, and it is believed
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