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Fulltext Divergent Solutions to Visual Problem Solving across Mammalian Species

Mustafar F, Harvey MA, Khani A, Arató J, Rainer G

eNeuro, 2018 07 11;5(4).
PMID: 30073190 DOI: 10.1523/ENEURO.0167-18.2018

Our understanding of the neurobiological underpinnings of learning and behavior relies on the use of invasive techniques, which necessitate the use of animal models. However, when different species learn the same task, to what degree are they actually producing the same behavior and engaging homologous neural circuitry? This question has received virtually no recent attention, even as the most powerful new methodologies for measuring and perturbing the nervous system have become increasingly dependent on the use of murine species. Here, we test humans, rats, monkeys, and an evolutionarily intermediate species, tree shrews, on a three alternative, forced choice, visual contrast discrimination task. As anticipated, learning rate, peak performance, and transfer across contrasts was lower in the rat compared to the other species. More interestingly, rats exhibited two major behavioral peculiarities: while monkeys and tree shrews based their choices largely on visual information, rats tended to base their choices on past reward history. Furthermore, as the task became more difficult, rats largely disengaged from the visual stimulus, reverting to innate spatial predispositions in order to collect rewards near chance probability. Our findings highlight the limitation of muridae as models for translational research, at least in the area of visually based decision making.

Matched MeSH terms: Macaca fascicularis
Fulltext [TRIMCyp frequency of the cynomolgus macaque (Macaca fascicularis) in captivity in China]

Tian S, Meng YH, Liu MY, Sun F, Chen JH, Du HL, et al.

Zool Res, 2013 Apr;34(2):97-102.
PMID: 23572358 DOI: 10.3724/SP.J.1141.2013.02097

In most Old world monkey species, TRIM5α plays a role in combating retroviruses and restricting HIV-1. Alongside TRIM5α, the TRIMCyp fusion gene formed by the retrotransposition of a CypA pseudogene cDNA to 3' terminal or 3'-UTR of TRIM5 gene in these monkeys has become a key research area in anti HIV-1 factors. The regional differences, gene frequencies, genotypes, and retrovirus restrictive activities of TRIMCyp vary among different primate species. While the frequencies of cynomolgus TRIMCyp have been studied in several areas of Southeast Asia, the frequency and prevalence of cynomolgus TRIMCyp in China remains unclear. In this study, we screened 1, 594 cynomolgus samples from 11 monkey manufacturers located across 5 provinces in China. Our results showed that the frequencies of TRIMCyp range from 7.65% to 19.79%, markedly lower than the frequencies found in monkey species in the Philippines, Malaysia and Indonesia (ranging from 34.85% to 100%). We speculate that potentially the latter were isolated groups established since 1978. The NE haplotype frequencies of cynomolgus TRIMCyp were 4.93% in China, also significantly lower than those found in species in the Philippines, Malaysia and Indonesia (from 11.1% to 14.3%). Our research provides interesting findings that contribute towards a more firm basis of further studies of HIV-1 animal models and relevant pathogenesis.

Matched MeSH terms: Macaca fascicularis/genetics*
Fulltext Phylogenetic relationships of Malaysia's long-tailed macaques, Macaca fascicularis, based on cytochrome b sequences

Abdul-Latiff MA, Ruslin F, Fui VV, Abu MH, Rovie-Ryan JJ, Abdul-Patah P, et al.

Zookeys, 2014.
PMID: 24899832 DOI: 10.3897/zookeys.407.6982

Phylogenetic relationships among Malaysia's long-tailed macaques have yet to be established, despite abundant genetic studies of the species worldwide. The aims of this study are to examine the phylogenetic relationships of Macaca fascicularis in Malaysia and to test its classification as a morphological subspecies. A total of 25 genetic samples of M. fascicularis yielding 383 bp of Cytochrome b (Cyt b) sequences were used in phylogenetic analysis along with one sample each of M. nemestrina and M. arctoides used as outgroups. Sequence character analysis reveals that Cyt b locus is a highly conserved region with only 23% parsimony informative character detected among ingroups. Further analysis indicates a clear separation between populations originating from different regions; the Malay Peninsula versus Borneo Insular, the East Coast versus West Coast of the Malay Peninsula, and the island versus mainland Malay Peninsula populations. Phylogenetic trees (NJ, MP and Bayesian) portray a consistent clustering paradigm as Borneo's population was distinguished from Peninsula's population (99% and 100% bootstrap value in NJ and MP respectively and 1.00 posterior probability in Bayesian trees). The East coast population was separated from other Peninsula populations (64% in NJ, 66% in MP and 0.53 posterior probability in Bayesian). West coast populations were divided into 2 clades: the North-South (47%/54% in NJ, 26/26% in MP and 1.00/0.80 posterior probability in Bayesian) and Island-Mainland (93% in NJ, 90% in MP and 1.00 posterior probability in Bayesian). The results confirm the previous morphological assignment of 2 subspecies, M. f. fascicularis and M. f. argentimembris, in the Malay Peninsula. These populations should be treated as separate genetic entities in order to conserve the genetic diversity of Malaysia's M. fascicularis. These findings are crucial in aiding the conservation management and translocation process of M. fascicularis populations in Malaysia.

Matched MeSH terms: Macaca fascicularis
Microfilarial granulomas in the spleens of wild-caught cynomolgus monkeys (Macaca fascicularis)

Narama I, Miura K, Tsuruta M, Tsuchitani M

Vet Pathol, 1985 Jul;22(4):355-62.
PMID: 4035940

Splenic nodules from 38 cynomolgus monkeys (Macaca fascicularis) which were captured in Malaysia and Indonesia were studied histologically. The lesions were characterized by well-circumscribed focal fibrosis, accumulation of eosinophils and histiocytes, hemorrhage or hemosiderosis, and loss of normal splenic architecture. Small arteries in the lesion frequently had intimal thickening and narrowing of the lumen in addition to the presence of microfilariae. Microfilariae were also seen in the extravascular area of the lesion, and were occasionally engulfed by multinucleated giant cells. The splenic lesion was thought to have been initiated by incomplete infarction caused by intimal thickening and microfilarial occupation of the small arteries.

Matched MeSH terms: Macaca fascicularis*
Construction of A Preliminary Three-Dimensional Structure Simian betaretrovirus Serotype-2 (SRV-2) Reverse Transcriptase Isolated from Indonesian Cynomolgus Monkey

Saepuloh U, Iskandriati D, Pamungkas J, Solihin DD, Mariya SS, Sajuthi D

Trop Life Sci Res, 2020 Oct;31(3):47-61.
PMID: 33214855 DOI: 10.21315/tlsr2020.31.3.4

Simian betaretrovirus serotype-2 (SRV-2) is an important pathogenic agent in Asian macaques. It is a potential confounding variable in biomedical research. SRV-2 also provides a valuable viral model compared to other retroviruses which can be used for understanding many aspects of retroviral-host interactions and immunosuppression, infection mechanism, retroviral structure, antiretroviral and vaccine development. In this study, we isolated the gene encoding reverse transcriptase enzyme (RT) of SRV-2 that infected Indonesian cynomolgus monkey (Mf ET1006) and predicted the three dimensional structure model using the iterative threading assembly refinement (I-TASSER) computational programme. This SRV-2 RT Mf ET1006 consisted of 547 amino acids at nucleotide position 3284-4925 of whole genome SRV-2. The polymerase active site located in the finger/palm subdomain characterised by three conserved catalytic aspartates (Asp90, Asp165, Asp166), and has a highly conserved YMDD motif as Tyr163, Met164, Asp165 and Asp166. We estimated that this SRV-2 RT Mf ET1006 structure has the accuracy of template modelling score (TM-score 0.90 ± 0.06) and root mean square deviation (RMSD) 4.7 ± 3.1Å, indicating that this model can be trusted and the accuracy can be seen from the appearance of protein folding in tertiary structure. The superpositionings between SRV-2 RT Mf ET1006 and Human Immunodeficiency Virus-1 (HIV-1) RT were performed to predict the structural in details and to optimise the best fits for illustrations. This SRV-2 RT Mf ET1006 structure model has the highest homology to HIV-1 RT (2B6A.pdb) with estimated accuracy at TM-score 0.911, RMSD 1.85 Å, and coverage of 0.953. This preliminary study of SRV-2 RT Mf ET1006 structure modelling is intriguing and provide some information to explore the molecular characteristic and biochemical mechanism of this enzyme.

Matched MeSH terms: Macaca fascicularis
Fulltext Lead Concentration in Long-Tailed Macaque (Macaca fascicularis) Hair in Kuala Selangor, Malaysia

Hassim NA, Hambali K, Idris NSU, Amir A, Ismail A, Zulkifli SZ, et al.

Trop Life Sci Res, 2018 Jul;29(2):175-186.
PMID: 30112148 MyJurnal DOI: 10.21315/tlsr2018.29.2.12

Long-tailed macaque (Macaca fascicularis) has the potential to be a good biological indicator for toxic exposure because they have an almost similar physiology and behaviour to humans. The objective of this study is to determine the concentration of lead (Pb) in hair samples of long-tailed macaques which were found in and out of the Kuala Selangor Nature Park (KSNP) area. The hypothesis is long-tailed macaques that live in the anthropogenic area (outside KSNP) may be exposed to high levels of lead compared to long-tailed macaques living in the forest area (inside KSNP). Analysis of hair samples were carried out using Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). The study found that the average mean of lead concentration in the anthropogenic area is 6.31 μg/g while for the forest area it is 3.16 μg/g. Lead concentration in the two areas are statistically insignificant. Nevertheless, lead concentration in the anthropogenic area recorded a slightly higher mean concentration than in the forest area. Even so, results of this study indicate that long-tailed macaques in Kuala Selangor are not exposed to high levels of lead. This study is the first in Malaysia to utilise long-tailed macaques as a biological indicator for testing the concentration of toxic substances in the environment. This study is still in its early stages; thus, future research requires improvements.

Matched MeSH terms: Macaca fascicularis
Fulltext The colonization of carrion by soldier fly, Ptecticus melanurus (Walker) (Diptera: Stratiomyidae) in a tropical forest in Malaysia: a new potential species for minimum PMI estimation

Azwandi A, Omar B

Trop Biomed, 2012 Dec;29(4):638-41.
PMID: 23202610

This paper discusses the colonization of the stratiomyid species Ptecticus melanurus (Walker) (Diptera: Stratiomyidae) in monkey carrion and its potential for the determination of the minimum time since death (PMI). A study was conducted in a tropical forest at Bangi, Malaysia from 13 November 2009 to 8 June 2011. Twelve monkey carcasses (Macaca fascicularis Raffles) were used and divided in equal number into three different field trials. Adults of P. melanurus were first observed on monkey carrions on the second day the carcasses were placed in the field while their penultimate instar larvae were found in the wet soil under and beside carcass from day 8 to 31 days postmortem.

Matched MeSH terms: Macaca fascicularis/parasitology*
Fulltext Predation on pupa of Chrysomya rufifacies (Marquart) (Diptera: Calliphoridae) by parasitoid, Exoristobia philippinensis Ashmead (Hymenoptera: Encyrtidae) and Ophyra spinigera larva (Diptera: Muscidae)

Chin HC, Ahmad NW, Lim LH, Jeffery J, Omar B, Dhang CC, et al.

Trop Biomed, 2009 Dec;26(3):369-72.
PMID: 20237454

A forensic entomological study was conducted using monkey carcasses (Macaca fascicularis Raffles) that were placed in either an outdoor or indoor environment at a coastal area in Tanjung Sepat, Selangor, Malaysia during May until August 2008. We collected pupae of Chrysomya rufifacies (Marquart) from the carcasses and kept them individually. The emergence of 13 parasitic microhymenopteran, from one of the pupae occurring within a week were identified as Exoristobia philippinensis Ashmead (Hymenoptera: Encyrtidae). Another observation was made whereby a pupa of C. rufifacies was predated by a muscid larva, Ophyra spinigera (Stein). The larva squeezed into the pupa and consumed the contents. This paper report C. rufifacies as a new host record for E. philippinensis in Malaysia and highlighted the predatory behavior of O. spinigera larva in natural environment.

Matched MeSH terms: Macaca fascicularis/parasitology*
Fulltext An observation on the decomposition process of gasoline-ingested monkey carcasses in a secondary forest in Malaysia

Rumiza AR, Khairul O, Zuha RM, Heo CC

Trop Biomed, 2010 Dec;27(3):373-83.
PMID: 21399577

This study was designed to mimic homicide or suicide cases using gasoline. Six adult long-tailed macaque (Macaca fascicularis), weighing between 2.5 to 4.0 kg, were equally divided into control and test groups. The control group was sacrificed by a lethal dose of phenobarbital intracardiac while test group was force fed with two doses of gasoline LD50 (37.7 ml/kg) after sedation with phenobarbital. All carcasses were then placed in a decomposition site to observe the decomposition and invasion process of cadaveric fauna on the carcasses. A total of five decomposition stages were recognized during this study. This study was performed during July 2007. Fresh stage of control and test carcasses occurred between 0 to 15 and 0 to 39 hours of exposure, respectively. The subsequent decomposition stages also exhibited the similar pattern whereby the decomposition process of control carcasses were faster than tested one. The first larvae were found on control carcasses after 9 hours of death while the test group carcasses had only their first blowfly eggs after 15 hours of exposure. Blow flies, Achoetandrus rufifacies and Chrysomya megacephala were the most dominant invader of both carcasses throughout the decaying process. Diptera collected from control carcasses comprised of scuttle fly, Megaselia scalaris and flesh fly, sarcophagid. We concluded that the presence of gasoline and its odor on the carcass had delayed the arrival of insect to the carcasses, thereby slowing down the decomposition process in the carcass by 6 hours.

Matched MeSH terms: Macaca fascicularis
Fulltext First report of the signal fly, Scholastes sp. (Diptera:Platystomatidae) visiting animal carcasses in Malaysia

Dhang CC, Heo CC, McAlpine D, Kurahashi H, Ahmad NW, Mohamad AM, et al.

Trop Biomed, 2008 Dec;25(3):264-6.
PMID: 19287370

Signal fly, Scholastes sp. (Diptera: Platystomatidae) was observed associated with animal carcasses in Malaysia. The first observation was on a monkey carcass, which was killed by using a handgun and immediately placed in a forested area in Gombak, Selangor while the second observation was on a pig that died of natural causes and whose carcass was placed in an oil palm plantation in Tanjung Sepat, Selangor. Both animal carcasses were visited by Scholastes sp. flies during the fresh decomposition period. However, the role Scholastes flies in the decomposition process remains unknown. In this paper, we report the occurrence of Scholastes sp. on animal carcasses in Malaysia for the first time.

Matched MeSH terms: Macaca fascicularis
Monkey malaria kills four humans

Galinski MR, Barnwell JW

Trends Parasitol, 2009 May;25(5):200-4.
PMID: 19345613 DOI: 10.1016/j.pt.2009.02.002

Four human deaths caused by Plasmodium knowlesi, a simian malaria species, are stimulating a surge of public health interest and clinical vigilance in vulnerable areas of Southeast Asia. We, and other colleagues, emphasize that these cases, identified in Malaysia, are a clear warning that health facilities and clinicians must rethink the diagnosis and treatment of malaria cases presumed to be caused by a less virulent human malaria species, Plasmodium malariae.

Matched MeSH terms: Macaca fascicularis/parasitology
Natural transmission of Plasmodium knowlesi to humans by Anopheles latens in Sarawak, Malaysia

Vythilingam I, Tan CH, Asmad M, Chan ST, Lee KS, Singh B

Trans R Soc Trop Med Hyg, 2006 Nov;100(11):1087-8.
PMID: 16725166

Four species of malaria parasites are known to infect humans. A fifth species, Plasmodium knowlesi, has been reported to infect humans in Malaysian Borneo. Here we report for the first time the incrimination of Anopheles latens as the vector of P. knowlesi among humans and monkeys in Sarawak, Malaysia.

Matched MeSH terms: Macaca fascicularis/parasitology
The value of potency testing of poliomyelitis and measles vaccines as an integral part of cold chain surveillance

Saraswathy TS, Sinniah M, Lee WS, Lee PC

Southeast Asian J. Trop. Med. Public Health, 1993 Jun;24(2):265-8.
PMID: 8266228

The Virology Division in the Institute for Medical Research, Kuala Lumpur, Malaysia performs potency tests on oral polio vaccines and live attenuated measles vaccines. Since these potency tests were introduced in 1981 a total of 752 tests have been performed on vaccine samples from peripheral immunization centers. Of 165 representative vaccine samples sent for potency evaluation after a cold chain breakdown 154 (87%) passed minimum potency requirements recommended for immunization of infants. In the absence of potency evaluation, those vaccines exposed to temperatures higher than the recommended storage range would be discarded, perhaps resulting in unnecessary wastage and economic loss. Results of the vaccine potency evaluation has enabled health authorities to indirectly monitor cold chain efficiency and ensure the high quality of viral vaccines used in our childhood immunization program.

Matched MeSH terms: Macaca fascicularis
Simian malaria infection in wild caught Macaca fascicularis and Presbytis spp in Malaysia

Rain AN, Mak JW, Zamri R

Southeast Asian J. Trop. Med. Public Health, 1993 Jun;24(2):386-7.
PMID: 8266247
Matched MeSH terms: Macaca fascicularis/parasitology*
Fulltext Approximate estimation of the condition of denervated muscle by studying intensity duration curves

Myint K, Nwe HH, Kanagasuntheram R

Med J Malaysia, 1982 Jun;37(2):175-9.
PMID: 7132838

Morphological and neuroelectrical changes of the skeletal muscle fibres after various types of injury to the nerve was studied in monkey. The percentage of normal and atrophic muscle fibres after various types of injury to the nerve was compared with the proportion of innervated and denervated muscle as shown by the position of the bend (kink) on the I.D. at corresponding stages. It was found that the pattern and the position of the I.D. curve when considered together only gave an approximate estimation of the proportion of all innervated and denervated muscle fibres as well as the condition ofthe muscle after denervation.

Matched MeSH terms: Macaca fascicularis
Fulltext Blunt force trauma to skull with various instruments

Sulaiman NA, Osman K, Hamzah NH, Amir SP

Malays J Pathol, 2014 Apr;36(1):33-9.
PMID: 24763233 MyJurnal

Deaths due to blunt force trauma to the head as a result of assault are some of the most common cases encountered by the practicing forensic pathologist. Previous studies have shown inflicting injury to the head region is one of the most effective methods of murder. The important factors that determine severity of trauma include the type of weapon used, type and site of skull fracture, intracranial haemorrhage and severity of brain injury. The aim of this study was to determine the characteristics of blunt force trauma to the skull produced by different instruments. Nine adult monkeys (Macaca fascicularis) skulls were used as models. Commonly found blunt objects comprising of Warrington hammer, hockey stick and open face helmet were used in this study. A machine calibrated force generator was used to hold the blunt object in place and to hit the skulls at forces of 12.5N and 25N. Resultant traumatic effects and fractures (linear, depressed, basilar, comminuted, and distastic) were analyzed according to type of blunt object used; surface area of contact and absolute force (N/cm(2)) delivered. Results showed that all investigated instruments were capable of producing similar injuries. The severity of trauma was not related to the surface area of contact with the blunt objects. However, only high absolute forces produced comminuted fractures. These findings were observational, as the samples were too small for statistical conclusions.

Matched MeSH terms: Macaca fascicularis
Fulltext The resin-embedded cornea prepared via rapid processing protocol : a good histomorphometric target for clinical investigation in ophthalmology and optometry

Cheah PS, Mohidin N, Mohd Ali B, Maung M, Latif AA

Malays J Med Sci, 2008 Jul;15(3):49-54.
PMID: 22570589

This study illustrates and quantifies the changes on corneal tissue between the paraffin-embedded and resin-embedded blocks and thus, selects a better target in investigational ophthalmology and optometry via light microscopy. Corneas of two cynomolgus monkeys (Macaca fascicularis) were used in this study. The formalin-fixed cornea was prepared in paraffin block via the conventional tissue processing protocol (4-day protocol) and stained with haematoxylin and eosin. The glutaraldehyde-fixed cornea was prepared in resin block via the rapid and modified tissue processing procedure (1.2-day protocol) and stained with toluidine blue. The paraffin-embedded sample exhibits various undesired tissue damage and artifact such as thinner epithelium (due to the substantial volumic extraction from the tissue), thicker stroma layer (due to the separation of lamellae and the presence of voids) and the distorted endothelium. In contrast, the resin-embedded corneal tissue has demonstrated satisfactory corneal ultrastructural preservation. The rapid and modified tissue processing method for preparing the resin-embedded is particularly beneficial to accelerate the microscopic evaluation in ophthalmology and optometry.

Matched MeSH terms: Macaca fascicularis
Fulltext Resistance of Cynomolgus Monkeys to Nipah and Hendra Virus Disease Is Associated With Cell-Mediated and Humoral Immunity

Prasad AN, Woolsey C, Geisbert JB, Agans KN, Borisevich V, Deer DJ, et al.

J Infect Dis, 2020 05 11;221(Suppl 4):S436-S447.
PMID: 32022850 DOI: 10.1093/infdis/jiz613

BACKGROUND: The henipaviruses, Hendra virus (HeV) and Nipah virus (NiV), are capable of causing severe and often lethal respiratory and/or neurologic disease in animals and humans. Given the sporadic nature of henipavirus outbreaks, licensure of vaccines and therapeutics for human use will likely require demonstration of efficacy in animal models that faithfully reproduce the human condition. Currently, the African green monkey (AGM) best mimics human henipavirus-induced disease.
METHODS: The pathogenic potential of HeV and both strains of NiV (Malaysia, Bangladesh) was assessed in cynomolgus monkeys and compared with henipavirus-infected historical control AGMs. Multiplex gene and protein expression assays were used to compare host responses.
RESULTS: In contrast to AGMs, in which henipaviruses cause severe and usually lethal disease, HeV and NiVs caused only mild or asymptomatic infections in macaques. All henipaviruses replicated in macaques with similar kinetics as in AGMs. Infection in macaques was associated with activation and predicted recruitment of cytotoxic CD8+ T cells, Th1 cells, IgM+ B cells, and plasma cells. Conversely, fatal outcome in AGMs was associated with aberrant innate immune signaling, complement dysregulation, Th2 skewing, and increased secretion of MCP-1.
CONCLUSION: The restriction factors identified in macaques can be harnessed for development of effective countermeasures against henipavirus disease.

Matched MeSH terms: Macaca fascicularis*
Fulltext Geographical, genetic and functional diversity of antiretroviral host factor TRIMCyp in cynomolgus macaque (Macaca fascicularis)

Saito A, Kono K, Nomaguchi M, Yasutomi Y, Adachi A, Shioda T, et al.

J Gen Virol, 2012 Mar;93(Pt 3):594-602.
PMID: 22113010 DOI: 10.1099/vir.0.038075-0

The antiretroviral factor tripartite motif protein 5 (TRIM5) gene-derived isoform (TRIMCyp) has been found in at least three species of Old World monkey: rhesus (Macaca mulatta), pig-tailed (Macaca nemestrina) and cynomolgus (Macaca fascicularis) macaques. Although the frequency of TRIMCyp has been well studied in rhesus and pig-tailed macaques, the frequency and prevalence of TRIMCyp in cynomolgus macaques remain to be definitively elucidated. Here, the geographical and genetic diversity of TRIM5α/TRIMCyp in cynomolgus macaques was studied in comparison with their anti-lentiviral activity. It was found that the frequency of TRIMCyp in a population in the Philippines was significantly higher than those in Indonesian and Malaysian populations. Major and minor haplotypes of cynomolgus macaque TRIMCyp with single nucleotide polymorphisms in the cyclophilin A domain were also found. The functional significance of the polymorphism in TRIMCyp was examined, and it was demonstrated that the major haplotype of TRIMCyp suppressed human immunodeficiency virus type 1 (HIV-1) but not HIV-2, whilst the minor haplotype of TRIMCyp suppressed HIV-2 but not HIV-1. The major haplotype of TRIMCyp did not restrict a monkey-tropic HIV-1 clone, NL-DT5R, which contains a capsid with the simian immunodeficiency virus-derived loop between α-helices 4 and 5 and the entire vif gene. These results indicate that polymorphisms of TRIMCyp affect its anti-lentiviral activity. Overall, the results of this study will help our understanding of the genetic background of cynomolgus macaque TRIMCyp, as well as the host factors composing species barriers of primate lentiviruses.

Matched MeSH terms: Macaca fascicularis/immunology*
Simian immunodeficiency virus SIVmac239 infection and simian human immunodeficiency virus SHIV89.6P infection result in progression to AIDS in cynomolgus macaques of Asian origin

Okamura T, Tsujimura Y, Soma S, Takahashi I, Matsuo K, Yasutomi Y

J Gen Virol, 2016 Dec;97(12):3413-3426.
PMID: 27902330 DOI: 10.1099/jgv.0.000641

Simian immunodeficiency virus (SIV) infection models in cynomolgus macaques are important for analysis of the pathogenesis of immunodeficiency virus and for studies on the efficacy of new vaccine candidates. However, very little is known about the pathogenesis of SIV or simian human immunodeficiency virus (SHIV) in cynomolgus macaques from different Asian countries. In the present study, we analysed the infectivity and pathogenicity of CCR5-tropic SIVmac and those of dual-tropic SHIV89.6P inoculated into cynomolgus macaques in Indonesian, Malaysian or Philippine origin. The plasma viral loads in macaques infected with either SIVmac239 or SHIV89.6P were maintained at high levels. CD4+ T cell levels in macaques infected with SIVmac239 gradually decreased. All of the macaques infected with SHIV89.6P showed greatly reduced CD4+ T-cell numbers within 6 weeks of infection. Eight of the 11 macaques infected with SIVmac239 were killed due to AIDS symptoms after 2-4.5 years, while four of the five macaques infected with SHIV89.6P were killed due to AIDS symptoms after 1-3.5 years. We also analysed cynomolgus macaques infected intrarectally with repeated low, medium or high doses of SIVmac239, SIVmac251 or SHIV89.6P. Infection was confirmed by quantitative RT-PCR at more than 5000, 300 and 500 TCID50 for SIVmac239, SIVmac251 and SHIV89.6P, respectively. The present study indicates that cynomolgus macaques of Asian origin are highly susceptible to SIVmac and SHIV infection by both intravenous and mucosal routes. These models will be useful for studies on virus pathogenesis, vaccination and therapeutics against human immunodeficiency virus/AIDS.

Matched MeSH terms: Macaca fascicularis

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