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National Research Council (US) Institute for Laboratory Animal Research. International Perspectives: The Future of Nonhuman Primate Resources. Washington (DC): National Academies Press (US); 2003.

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International Perspectives: The Future of Nonhuman Primate Resources.

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Indian- and Chinese-origin Rhesus Macaques for AIDS-related Research: Comparison of Vaginal Transmission Efficiency of Simian Immunodeficiency Virus (SIV), Viral Loads, and Virus-specific Antibody Responses

Marta L. Marthas, PhD,*, Ding Lu,* M. C. T. Penedo,§ Andrew G. Hendrickx,* and Christopher J. Miller,*,,#

INTRODUCTION

The use of rhesus macaques as a nonhuman primate model for human HIV infection and AIDS has resulted in an unprecedented demand that has far exceeded the supply of domestically bred animals; thus, researchers must use monkeys from other sources. Most domestically bred rhesus macaques are derived from animals imported from India. Because Indian macaques can no longer be exported, China has become one of the most reliable sources for rhesus macaques. However, it has been reported that the clinical course of SIV infection is slower and more variable in Chinese-origin monkeys compared with Indian origin monkeys (Joag and others 1994). We designed a study to determine whether Chinese-origin rhesus monkeys are more resistant to infection after intravaginal (IVAG) SIV inoculation compared with Indian-origin rhesus macaques (Marthas and others 2001). The findings of this recently published study are summarized below.

RESULTS AND DISCUSSION

We found no significant difference in the number of animals infected after one or two IVAG inoculations for Indian-origin compared with Chinese-origin macaques. Thus, rhesus monkeys originating from both countries are useful for studies requiring SIV transmission and infection. However, consistent with results of our previous studies, two IVAG doses of SIV resulted in significantly more SIV-infected macaques than one IVAG inoculation (Miller and others 1990, 1992).

We also compared the level of viremia in SIV infection in Chinese-and Indian-origin rhesus monkeys during the first few weeks of infection. As previously reported, SIV RNA levels in plasma among SIV-infected macaques were variable, and the variation was greater among the Indian-origin than among the Chinese-origin rhesus monkeys. SIV RNA levels at 2 weeks postinfection (PI) in plasma of Chinese- and Indian-origin animals were found to be high but not significantly different. However, by 6 weeks PI, the plasma SIV RNA levels were significantly lower in Chinese-compared with Indian-origin rhesus macaques, despite large overlap in the range of viral loads among Indian- and Chinese-origin animals. Our result is consistent with earlier observations from smaller numbers of Chinese and Indian rhesus macaques inoculated parenterally with SIV (Joag and others 1994).

Anti-SIV plasma antibody levels were also more variable in the Indian-origin rhesus macaques; however, at 6 to 8 weeks PI, there were no significant differences in SIV-antibody titers for Chinese- and Indian-origin rhesus macaques. It is well documented that Indian-origin rhesus monkeys that fail to make an antibody response to SIV or SHIV infection have a rapid disease course (Daniel and others 1987; Kimata and others 1999; Lewis and others 1994; Lu and others 1998). Our study found that rapid progression to AIDS (i.e., within 3 months PI) occurs at similar frequency in SIV-infected rhesus monkeys of Chinese-origin (1 of 10) and Indian-origin (1 of 16).

We used a panel of 13 highly polymorphic microsatellite markers to assess the degree of genetic similarity between monkeys of Chinese and Indian origin. Consistent with expectations for geographically separate populations of a single polymorphic species, we detected the majority of alleles for the 13 microsatellite loci in both Indian-origin and Chinese-origin animals; however, some allele frequencies differed among Indian-and Chinese-origin animals as reported previously (Morin and others 1997). We found no microsatellite alleles that were diagnostic for Chinese or Indian origin.

Overall, we found that the geographic origin of rhesus macaques does not predict the efficiency of vaginal SIV transmission or the level of SIV RNA in plasma of SIV-infected animals during the first few weeks after IVAG inoculation. Most importantly, our results demonstrate that both Chinese-origin and Indian-origin rhesus macaques are well suited for AIDS-related studies that require mucosal SIV infection.

ACKNOWLEDGMENTS

This work was supported by Public Health Service grant RR00169 from the National Center for Research Resources; grants AI39109 (M.L.M), AI39435 (C.J.M), and AI35545 (C.J.M) from the National Institute of Allergy and Infectious Diseases; and Elizabeth Glaser Scientist award 8-97 (M.L.M) from the Elizabeth Glaser Pediatric AIDS Foundation.

REFERENCES

  • Daniel M.D., N.L. Letvin, P.K. Sehgal, G. Hunsmann, D.K. Schmidt, N.W. King, and R.C. Desrosiers. 1987. Long-term persistent infection of macaque monkeys with the simian immunodeficiency virus. J Gen Virol 68:3183-3189. [PubMed: 2826656]
  • Joag S. V., E.B. Stephens, R.J. Adams, L. Foresman, and O. Narayan. 1994. Pathogenesis of SIVmac infection in Chinese and Indian rhesus macaques: Effects of splenectomy on virus burden. Virology 200:436-446. [PubMed: 8178433]
  • Kimata J.T., L. Kuller, D.B. Anderson, P. Dailey, and J. Overbaugh. 1999. Emerging cytopathic and antigenic simian immunodeficiency virus variants influence AIDS progression. Nat Med 5:535-541. [PubMed: 10229230]
  • Lewis M., S. Bellah, K. McKinnon, J. Yalley-Ogunro, P. Zack, W. Elkins, R. Desrosiers, and G. Eddy. 1994. Titration and characterization of two rhesus-derived SIVmac challenge stocks. AIDS Res Hum Retrovirus 10:213-292. [PubMed: 8198874]
  • Lu Y., C.D. Pauza, X. Lü, D.C. Montefiori, and C.J. Miller. 1998. Rhesus macaques that become systemically infected with pathogenic SHIV 89.6-PD after intravenous, rectal, or vaginal inoculation and fail to make an antiviral antibody response rapidly develop AIDS. J AIDS Hum Retrovir 19:6-18. [PubMed: 9732063]
  • Marthas M.L., D. Lu, M.C. Penedo, A.G. Hendrickx, and C.J. Miller. 2001. Titration of an SIVmac251 stock by vaginal inoculation of Indian and Chinese origin rhesus macaques: transmission efficiency, viral loads, and antibody responses. AIDS Res Hum Retrovirus 17:1455-1466. [PMC free article: PMC3401017] [PubMed: 11679158]
  • Miller C., N. Alexander, A. Gettie, A. Hendrickx, and P. Marx. 1992. The effect of contraceptives containing nonoxynol-9 on the genital transmission of simain immunodeficiency virus in rhesus macaques. Fertil Steril 57:1126-1128. [PubMed: 1315297]
  • Miller C., N. Alexander, S. Sutjipto, S. Joye, A. Hendrickx, M. Jennings, and P. Marx. 1990. Effect of virus dose and nonoxynol-9 on the genital transmission of SIV in rhesus macaques. J Med Primatol 19:401-409. [PubMed: 2172544]
  • Morin P.A., S. Kanthaswamy, and D.G. Smith. 1997. Simple sequence repeat (SSR) polymorphisms for colony management and population genetics in rhesus macaques (Macaca mulatta). Am J Primatol 42:199-213. [PubMed: 9209585]

Footnotes

*

California National Primate Research Center

Department of Veterinary Pathology, Microbiology and Immunology

§

Center for Comparative Medicine

#

Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California, Davis, California

Copyright 2003 by the National Academy of Sciences. All rights reserved.
Bookshelf ID: NBK221784

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