Group D simian retroviruses (SRV)

Test codes:
P0001 - Ultrasensitive qualitative screen for SRV type D serogroups 1, 2, 3, 4, 5 and 8 by real time polymerase chain reaction
P0027 - Ultrasensitive qualitative screen for RNA of SRV type D serogroups 1, 2, 3, 4, 5 and 8 by reverse transcription coupled real time PCR
S0001 - Ultrasensitive qualitative detection of SRV-1 by real time polymerase chain reaction
S0002 - Ultrasensitive qualitative detection of SRV-2 by real time polymerase chain reaction
S0003 - Ultrasensitive qualitative detection of SRV-3 by real time polymerase chain reaction
S0004 - Ultrasensitive qualitative detection of SRV-5 by real time polymerase chain reaction

Simian retrovirus (SRV) types 1-5 and 8 are pathogenic betaretroviruses causing potentially fatal immunosuppressive disease (SAIDS) in captive Asian macaques. They are often identified in primate research centers. Simian AIDS, neoplasms, retroperitoneal fibromatosis (RF), and subcutaneous fibrosarcomas (SF) have been found in macaques infected with type D retroviruses.

SRV-2 is most commonly found in association with RF, and about 35% of SRV-2-infected macaques develop RF. SRV-1 and SRV-8 have also been linked to RF in some cases. SF is found in association with multiple serotypes, including SRV-1 and SRV-2, but less than 5% of infected monkeys develop SF. SRV-3, SRV-4, SRV-5, and SRV-8 are similarly associated with immunodeficiency syndromes, hematological abnormalities (such as anemia and leukopenia), and other AIDS-like symptoms, though their specific disease profiles can vary by host species and strain. RF in macaques is a potential model for human disease since the lesions in macaques are similar to idiopathic RF described in humans. Thus far, RF has not been found in species other than macaque and human.

SRV-3, also know as Mason–Pfizer monkey virus (MPMV), is a primate retrovirus that was first detected by electron microscopy in a mammary carcinoma of a female rhesus macaque, from which it was molecularly cloned and characterized. Newborn rhesus macaques experimentally inoculated with this prototypic D-type retrovirus develop a wasting disease within a few weeks that is accompanied by opportunistic infections including pneumonia, enteritis and rashes.

SRV-4 was first characterized at the Tsukuba Primate Center in Japan and is also referred to as SRV-Tsukuba.

SRV-5 contains a single prototype virus, D5/RHE/OR, isolated from rhesus macaques imported to the Oregon Primate Research Center from the People's Republic of China; this isolate produces severe immunodeficiency when transmitted into juvenile rhesus macaques.

Proposed serotypes SRV-6 and SRV-7 are less studied than other SRV serotypes as they are thought to occur only in wild Indian populations rather than captive U.S. or European primate centers. Full genome sequences of these two viruses are not available, and it has not been demonstrated that these viruses are actually genetically distinct from other simian retroviruses

For reasons of occupational safety and animal health, as well as to improve the quality of nonhuman primates used in biomedical research, the establishment and maintenance of specific retrovirus-free breeding colonies of macaques (genus Macaca) are high priorities. The current testing algorithm for this group of retroviruses includes routine direct virus detection in addition to antibody screening, as some SRV-infected animals lack disease symptoms and detectable antibodies, or exhibit a prolonged interval between infection and seroconversion. This parallel testing for SRV antibody and virus is critical, especially during primary screening of potential specific pathogen-free stock obtained from external sources. "Indeterminate" immunoblot results for this group of viruses continue to pose a problem of interpretation, and serological testing for group D retroviruses has a high false positive rate (Chen, 1992). Cross-reactivity is a major source of false positives in SRV testing by serology (Benveniste, 1993). The frequency of false negatives is also unacceptably high when serological testing alone is used. It has been found that antibody levels can vary in inverse proportion to viral titres, so that clinically asymptomatic animals with very low antibody levels may actually be highly viremic (Rosenblum, 2000). Even the combination of serology with viral culture results in significant false negative levels (Lerche, 1997).

Although a combination of serological testing and western blot can reduce but not eliminate false positives, western blots are generally too costly for use in ongoing screening and monitoring programs. In contrast, PCR amplification of proviral DNA has been found to be effective for the detection of the presence of SRV. In combination with antibody testing, detection of SRV by PCR is a rapid, specific, cost-effective and sensitive technique for the development and maintenance of specific pathogen free colonies.

Utilities:

• Establish diagnosis of retroviral infection
• Rapid screening to maintain research subjects free of SRV
• Differentiate SRV subtypes if necessary (using S-prefix tests listed above)
• Safety monitoring of experimental subjects
• Safety monitoring of biological products and vaccines that derive from primates
• Prevent further spread of viruses by identifying affected nonhuman primates

References:
Benveniste R.E., Hill R.W., Knott W.B., Tsai C.C., Kuller L., Morton W.R. (1993). Detection of serum antibodies in Ethiopian baboons that cross-react with SIV, HTLV-I, and type D retroviral antigens. J Med Primatol. 22(2-3):124-128.

Chen Z., Ben K., Tian B., Zheng Y. (1992). Serological survey of a captive macaque colony in China for antibodies to simian type D retroviruses. J Med Primatol. 21(7-8):377-380.

Lerche N.W., Cotterman R.F., Dobson M.D., Yee J.L., Rosenthal A.N., Heneine W.M. (1997). Screening for simian type-D retrovirus infection in macaques, using nested polymerase chain reaction. Lab Anim Sci. 47(3):263-268.

Lerche NW. Simian retroviruses: infection and disease--implications for immunotoxicology research in primates. J Immunotoxicol. 2010 Apr-Jun;7(2):93-101.

Liska V, Lerche NW, Ruprecht RM. Simultaneous detection of simian retrovirus type D serotypes 1, 2, and 3 by polymerase chain reaction. AIDS Res Hum Retroviruses. 1997 Mar 20;13(5):433-7.

Rosenblum L.L., Weiss R.A., McClure M.O. (2000). Virus load and sequence variation in simian retrovirus type 2 infection. Journal of Virology 74(8):3449-3454.

Specimen requirement: 0.5 ml whole blood in EDTA (purple top) tube.

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.

Turnaround time: 2 business days

Methodologies:
P0001, S0001, S0002, S0003 and S0004 - Qualitative real time PCR
P0027 - Qualitative reverse transcription coupled real time PCR

Normal range: Nondetected