TOWARDS SUCCESSFUL ADAPTATION OF PLASMODIUM KNOWLESI TO LONG-TERM IN-VITRO CULTURE IN HUMAN ERYTHROCYTES

TOWARDS SUCCESSFUL ADAPTATION OF PLASMODIUM KNOWLESI TO LONG-TERM IN-VITRO CULTURE IN HUMAN ERYTHROCYTES

F. S. Mohamad and N. Abu-Bakar ^*

School of Health Sciences, Health Campus, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia.

ABSTRACT: Plasmodium knowlesi, a simian malaria parasite, is widely used as a malaria model and now characterized as a clinically significant parasite that can lead to outbreaks throughout most countries in Southeast Asia. Despite its importance, both fundamental and clinical studies of P. knowlesi have been impeded by the lack of a convenient in-vitro culture system partly due to the parasite’s preference for reticulocytes. Due to a limited number of reticulocytes that could be collected from fresh sources such as umbilical cord, bone marrow, and peripheral blood, scientists have opted reticulocytes generated from CD34⁺ hematopoietic stem cells (HSCs) that have been cultured in an in-vitro system. With sufficient growth factors (GFs) and differentiation factors (DFs), a higher number and more homogenous populations of reticulocytes could be obtained from HSCs in-vitro. Here, we review an approach to produce massive expansion of CD34⁺ HSCs and their differentiation into reticulocytes that could be used for the establishment of a continuous in-vitro culture of P. knowlesi or P. vivax. The successful development of the long-term in-vitro culture of this parasite could ultimately provide an ideal system for forwarding diagnostic, anti-malarial drug and vaccine studies in malaria.

Plasmodium knowlesi, CD34⁺ hematopoietic stem cells, Reticulocytes, Erythrocytes, Parasite invasion

INTRODUCTION: Despite years of tremendous elimination efforts and progress, malaria remains as one of the most significant life-threatening diseases affecting people in tropical and subtropical regions. The World Malaria report 2017 reported that about 3.2 billion people were at risk of malaria, which accounts for nearly half of the world’s population. In 2016 alone, there were roughly 216 million malaria cases, an increase of 5 million cases over the previous year, an estimated 445,000 malaria deaths ¹.

In the same year, Malaysia reported 2,327 malaria cases, which occurred mostly in Malaysian Borneo; Sabah and Sarawak, as well as in other states in Peninsular Malaysia such as Kelantan, Perak and Selangor ².

Malaria is caused by hemoprotozoa from Plasmodium species and spread to humans through the bites of infected female Anopheles mosquitoes. P. falciparum is the most prevalent malaria parasite in sub-Saharan Africa, but outside of Africa, P. vivax is the predominant parasite in the region of the Americas, the Eastern Mediterranean and Southeast Asia ¹. In most endemic areas in Southeast Asia, P. knowlesi has been reported to cause a majority of malaria cases ³. According to the WHO Meeting report 2017, Malaysia recorded the highest burden of P. knowlesi (69% of total reported cases, mostly mono-infection) in 2016, which mostly affected men than women (about 80%) with more cases occurred among adults aged over 55 years old ². P. knowlesi cases were mostly reported in Sabah and Sarawak of Malaysian Borneo and other states of Peninsular Malaysia including Kelantan, Pahang, Johor, Terengganu, Selangor, Kedah, Penang, Perak and Melaka ^{1, 4, 5, 6, 7, 8}. The natural hosts of P. knowlesi are long-tailed (Macaca fascicularis) and pig-tailed (Macaca nemestrina) macaques ^{9, 10, 11, 12}. Warren et al., (1970) stated that knowlesi malaria was a rare zoonosis of humans after the first description of P. knowlesi human infection was revealed in 1965 by Chin et al., (1965) ^{13, 14}.

However, more human cases of this simian parasite have been identified after a large focus of apparent P. malariae cases in Kapit, Sarawak was investigated by Singh et al., (2004) using a molecular technique ¹⁵. By microscopic examination, a band form appearance of late trophozoites of P. knowlesi has been frequently misdiagnosed as P. malariae, and its early trophozoites have frequently been misidentified as P. falciparum due to similar characteristics such as the presence of double chromatin dots, multiple - infected erythrocytes and appliqué forms ^{16, 17, 18, 19}. Since P. knowlesi is now the dominant malaria parasite infecting humans in Southeast Asia and two times more prevalent than P. falciparum or P. vivax ⁷, if left untreated, it can result in a severe or fatal disease characterized by acute renal failure, acute respiratory distress syndrome and shock ^{20, 21}. Therefore, knowlesi malaria has become one of the healthcare emergencies in most Southeast Asian countries including Malaysia ²².

Studies of many aspects of P. knowlesi biology have posed an increasingly important challenge. This is partly due to the need to grow the parasite in its macaque host or in-vitro using macaque blood ^{17, 23, 24}. These requirements have restricted studies to laboratories with access to macaques or macaque blood. The recent attempt to grow and proliferate P. knowlesi in-vitro in human red blood cells (RBCs) is, therefore, a substantial step towards expanding research on P. knowlesi ^{17, 25, 26}. In this review, we discuss technical developments of the P. knowlesi in-vitro culture system and how this system can be developed based on a few current approaches that have been used thus far. We also highlight future potentials of the available human-adapted P. knowlesi parasite lines.

Establishment of the Continuous in-vitro Culture of P. knowlesi: Since the maintenance of P. knowlesi in-vitro in rhesus RBCs for several intraerythrocytic cycles was achieved in 1945, ²⁷ attempts to develop a continuous in-vitro culture for this malaria parasite have never ended ²⁸. The long-term in-vitro culture system would allow full analysis of parasite-host cell interactions ²⁹, improve understanding of the biology of P. knowlesi such as the mechanism of invasion ^{30, 31} and resistance markers ³², and contribute to the development of new anti-malarial drugs and vaccines ^{31, 33, 34, 35}. The study by Ball et al., (1945) indicated that target cells of P. knowlesi are not restricted to a certain age in macaques, however, in humans, it was found that P. knowlesi mainly invades reticulocytes ^{17, 27}. Previous attempts showed that P. knowlesi failed to be maintained exclusively in human blood ^{25, 29}.

The direct culture in 100% human RBCs resulted in very low growth rates and a complete loss of parasites within a week ²⁵. Similarly, Lim et al., (2013) showed that P. knowlesi was poorly proliferated in pooled human blood and had a decreased invasion efficiency into older RBCs ³⁶. Thus, the predilection for reticulocytes has been a major obstacle to establish a continuous in-vitro culture for P. knowlesi as these young RBCs circulate in peripheral blood at a very low concentration (0.5-1% of total RBCs) and for a very short time (24 h) ²⁶. Besides, a large quantity of reticulocytes is required to maintain a continuous culture and obtain an efficient parasite invasion. It was evidenced when P. knowlesi was cultured in blood enriched with more than 8% reticulocytes, increasing parasitemia and propagation ³⁶. The continuous culture was also successfully established and maintained for up to six months.

Potential Use of CD34⁺ Hematopoietic Stem Cell (HSC)-Derived Reticulocytes for Continuous in-vitro Culture of P. knowlesi: As reticulocytes represent only 0.5-1% of total RBCs in the bloodstream and have a short lifespan prior to maturation ²⁶, collecting sufficient reticulocytes from peripheral blood (PB) to maintain a P. knowlesi or P. vivax culture in-vitro is nearly impossible ²⁸. P. vivax has been shown to have a close phylogenetic relationship to P. knowlesi ³⁷. Furthermore, techniques to concentrate reticulocytes collected from PB using percoll centrifugation, several washing and concentration steps could damage the cells, thus affect invasion efficiency ^{34, 38}.

In an attempt to overcome this hurdle, several approaches have used hematopoietic stem cells (HSCs) isolated from either umbilical cord blood (UCB), bone marrow (BM) or PB as potential resources to generate higher production of reticulocytes in-vitro for parasite invasion ^{26, 34, 39, 40}. The culture systems include the application of specific cytokines and either co-culture the HSCs with feeder cells (i.e., human mesenchymal stem cells) ^{41, 42, 43, 44} to mimic the medullar micro-environment or without feeder cells ^{43, 45}. With sequential addition of specific growth factors (GFs) such as stem cell factors (SCF), interleukin-3 (IL-3), hydrocortisone and erythropoietin (EPO) in CD34⁺ HSC differentiation medium, the parasite culture could be maintained for a longer period in the presence of reticulocytes derived from CD34⁺ HSCs ^{34, 39}.

Although HSC - derived reticulocytes need approximately two weeks to mature rather than the use of immediately available reticulocytes, the former resource assures a more homogeneous and standardized cell population ^{34, 46, 47}. Furuya and his colleagues have improved the method of HSC culture to produce a higher percentage of reticule-cytes by using cryopreserved erythroblasts frozen after 8-day cultivation of UCB-isolated HSCs. The method allows the recovery of reticulocytes in a shorter time than with continuous stem cell culture. Moreover, a substantial number of reticulocytes (up to 0.8% of the total cells) are successfully invaded by P. vivax following 24 h post-cultivation ⁴⁸. Due to the similarities between P. knowlesi and P. vivax regarding their invasion pathways ³³, genetics ^{49, 50}, hosts and target cells ^{51, 52}, these approaches would provide insights into the development of long-term in-vitro culture system for P. knowlesi.

Cryopreservation of Reticulocytes and Malaria Parasite Isolates: Cryopreservation is a process of preserving the biological function of intact living cells or tissues by freezing and storing the material below -80 °C typically at or near the temperature of liquid nitrogen (-196 °C) ⁵³. This technique has been used in Plasmodium studies to allow research to be carried out in laboratories with limited access to fresh parasite isolates ⁵⁴. This technique facilitates more research groups working on this field and increases chances for major discoveries ⁵⁵. Among the cryopreservation solutions that have been used in previous studies are glycerolyte solution, medium containing glycerol and sorbitol, and IMDM/10% DMSO/40% FCS solution ^{48, 56}.

Noulin et al., (2012) reported a reliable cryo-preservation protocol for HSC-derived reticulocytes that could be invaded by cryopreserved P. vivax or P. falciparum isolates. More than 70% of cryopreserved cells were remained viable and stable compared to the control cells measured before cryopreservation ³⁴. Another study by Borlon et al., (2012) showed that the invasion efficiency of both cryopreserved parasite isolates and reticulocytes was similar to those obtained with fresh samples. They were also able to maintain the culture for up to 10 days ⁵⁴. These findings show that cryopreservation of reticulocytes did not affect cell stability as they matured normally and were still viable and able to support parasite growth and invasion ^{34, 54}. The cryopreservation method could be easily replicated in laboratories outside endemic areas and substantially contribute to the development of a continuous in-vitro culture of P. knowlesi in the future.

Invasion Mechanism of P. knowlesi: The invasion mechanism of P. knowlesi involves the interaction of a specific ligand presented on the merozoite surface known as Duffy binding proteins (DBPs) ⁵⁷ and a receptor available on human RBCs namely Duffy antigen receptor for chemokines (DARC) ⁵⁸. The invasion depends largely on the availability of DARC because no invasion was observed in Duffy-negative RBCs ²⁵. The level of DARC on mature RBCs is reduced compared to that on reticulocytes ²⁵, which possibly explains the predilection of P. knowlesi for reticulocytes. Besides Duffy binding protein, the reticulocyte binding-like proteins (RBLs), another important ligand family, also contribute to the successful invasion of human RBCs ^{49, 59}.

The RBL proteins expressed by P. knowlesi merozoites have been identified as normocyte binding proteins, PkNBPXa and PkNBPXb ^{57, 60, 61}. Unlike PkNBPXb, PkNBPXa binds to not only macaque cells but also human RBCs ⁶⁰. Therefore, the availability of human-adapted P. knowlesi line would provide a platform to elucidate the invasion mechanism and hence, facilitates in the improvement of strategies to control knowlesi malaria.

The Similarities of P. knowlesi and P. vivax: P. knowlesi is an ideal model for better understanding the various biological aspects of P. vivax (e.g., genetics, invasion and relapse mechanism, drug resistance) ^{17, 62}. Historically, P. knowlesi shares a few common biological aspects with P. vivax; both parasites were found to invade mainly human reticulocytes ⁶³ and use DARC to invade the reticulocytes ⁶². The gene sequence of P. knowlesi and P. vivax showed a near perfect synteny scattered with expansions of species-specific genes ^{37, 64}. Thus, in-depth study of P. knowlesi could provide an insight into P. vivax biology and the subsequent discovery of diagnostic tools, drugs and vaccines ^{17, 62}.

Adaptation of P. knowlesi to Continuous in-vitro Culture in Human Erythrocytes: Many attempts have been made to adapt P. knowlesi to stably proliferate in human RBCs in-vitro. However, due to its low replication rates, P. knowlesi has failed to stably grow in human RBCs alone ⁶⁵. This obstacle has been overcome by slowly growing P. knowlesi in a mixture of macaque and human RBCs ^{25, 36}. Following an initial adaptation in human RBCs, the parasites proliferation rates increased further from 2 fold to 5 fold per day ²⁵. In their report, Moon and his colleagues managed to produce one human-adapted P. knowlesi line known as P. knowlesi A1.H1 (PkA1-H.1) line that has been successfully adapted to continuous culture in-vitro, providing an in-vitro model suitable for further study on P. knowlesi. A major step towards adaptation involves a change in host cell preference for invasion ²⁵.

While not restricted to cells of a certain age in macaques, P. knowlesi was found to invade mainly young RBCs in humans. In contrast, the human-adapted line had increased invasion efficiency into older RBCs, providing access to a wider range of suitable host cells ^{17, 25}. The invasion of adapted P. knowlesi lines were still DARC dependent ²⁵. However, further investigation is necessary on the exact receptors involved in the later stage of invasion as the DARC level on blood cells diminishes as they mature ¹⁷. Therefore, the availability of human RBC-adapted P. knowlesi lines and the analyses of adaptation mechanism would enable the understanding of the parasite biology and the pathophysiology of knowlesi malaria in humans.

The Implications of Adaptation Success to Malaria Study: A successful establishment of continuous P. knowlesi in-vitro culture and adaptation in human RBCs would offer an ideal system for various implications to malaria research. The development of several advanced tools and technologies for use in other Plasmodium studies such as P. falciparum could be readily adapted for use in P. knowlesi ¹⁷. The application of advanced microscopy technologies such as real-time imaging of invasion 66, super-resolution microscopy ⁶⁷ and long-term live microscopy ¹⁷ to the P. knowlesi system will be particularly fruitful. The combination of high transfection efficiency and the ability to culture P. knowlesi in human RBCs will be ideal for the establishment of high-throughput analysis of gene functions ²⁹ and novel reverse genetics, which can be used to investigate the role of RBC receptors in P. knowlesi invasion ⁶⁸.

The application of several knockout/knockdown systems such as ligand-regulatable FKBP protein destabilization domains (ddFKBP) ^{69, 70} and the DiCre conditional recombinase system ⁷¹ in P. knowlesi will be beneficial in determining the functions of essential blood stage proteins. Likewise, high-efficiency genome editing tools such as TALEN (transcription activator-like effector nucleases) ⁷², CRISPR (clustered regularly interspaced short palindromic repeat)-Cas system ⁷³ and zinc-finger nucleases ⁷⁴ could be used to facilitate genomic integration of DNA constructs in P. knowlesi ¹⁷.

Also, human RBC-adapted P. knowlesi would allow a comprehensive study of invasion mechanism hence would prevent infection and suppress re-emergent blood stage parasite via the development of new anti-malarial drugs and vaccines ^{36, 75, 76}. Taken together, malaria research could be expanded further following successful adaptation and development of a long-term P. knowlesi in-vitro culture.

ACKNOWLEDGEMENT: We would like to thank Universiti Sains Malaysia (USM) for the Research University Grant given (USM RUI Grant No. 1001/PPSK/812201).

CONFLICT OF INTEREST: The authors declare no conflict of interest.

REFERENCES:

1. World Health Organization: World Malaria Report 2017. Geneva: World Health Organization, 2017.
2. World Health Organization Regional Office for the Western Pacific: Expert Consultation on Plasmodium knowlesi Malaria to Guide Malaria Elimination Strategies, Kota Kinabalu, Malaysia, 1-2 March 2017: Meeting Report. Manilla: World Health Organization Regional Office for the Western Pacific, 2017.
3. Grigg MJ, William T, Barber BE, Rajahram GS, Menon J, Schimann E, Piera K, Wilkes CS, Patel K, Chandna A, Drakeley CJ, Yeo TW and Anstey NM: Age-related clinical spectrum of knowlesi malaria and predictors of severity. Clinical Infectious Diseases 2018; 6: 1-10.
4. Cox-Singh J, Davis TM, Lee KS, Shamsul SS, Matusop A, Ratnam S, Rahman HA, Conway DJ and Singh B: Plasmodium knowlesi malaria in humans is widely distributed and potentially life-threatening. Clinical Infectious Diseases 2008; 46: 165-171.
5. Millar SB and Cox-Singh J: Human Infections with Plasmodium knowlesi - zoonotic malaria. Clinical Micro-biology and Infection 2015; 21: 640-48.
6. Divis PCS, Lin LC, Rovie-Ryan JJ, Kadir KA, Anderios F, Hisam S, Sharma RSK, Singh B and Conway DJ: Three divergent subpopulations of the malaria parasite knowlesi. Emerging Infectious Disease 2017; 23: 616-24.
7. Yusof R, Ahmed MA, Jelip J, Hie UN, Mustakim S, Hussin HM, Mun YF, Mahmud R, Frankie ATS, Japning JR-R, Snounou G, Escalante AA and Yee LL: Phylogeographic evidence for 2 genetically distinct zoonotic Plasmodium knowlesi parasites, Malaysia. Emerging Infectious Diseases 2016; 22: 1371-80.
8. Yong ASJ, Navaratnam P, Kadirvelu A and Pillai N: Re-emergence of malaria in Malaysia: A review article. Open Access Library Journal 2018; 5: e4298.
9. Knowles R and Das Gupta B: A study of monkey-malaria and its experimental transmission to man. The Indian Medical Gazette 1932; 20: 237-47.
10. Subbarao SK: Centenary celebrations article: Plasmodium knowlesi: from macaque monkeys to humans in Southeast Asia and the risk of its spread in India. Journal of Parasitic Diseases 2011; 35: 87-93.
11. Ahmed MA and Cox-Singh J: Plasmodium knowlesi - an emerging pathogen. ISBT Science Series 2015; 10: 134-40.
12. Zhang X, Kadir KA, Quintanilla-Zariñan LF, Villano J, Houghton P, Du H, Singh B and Smith DG: Distribution and prevalence of malaria parasites among long-tailed macaques (Macaca fascicularis) in regional populations across Southeast Asia. Malaria Journal 2016; 15: 450.
13. Warren H, Cheong WH, Fredericks HK and Coatney GR: Cycles of jungle malaria in West Malaysia. American J of Tropical Medicine and Hygiene 1970; 19: 383-93.
14. Chin W, Contacos PG, Coatney GR and Kimball HR: A naturally acquired quotidian-type malaria in man transferable to monkeys. Science 1965; 149: 865-69.
15. Singh B, Kim Sung, L, Matusop A, Radhakrishnan A, Shamsul SS, Cox-Singh J, Thomas A and Conway DJ: A large focus of naturally acquired Plasmodium knowlesi infections in human beings. Lancet 2004; 363: 1017-24.
16. Barber BE, Grigg MJ, William T, Yeo TW and Anstey NM: The treatment of Plasmodium knowlesi Trends in Parasitology 2016; 33: 242-53.
17. Grüring C, Moon RW, Lim C, Holder AA, Blackman MJ and Duraisingh MT: Human red blood cell-adapted Plasmodium knowlesi parasites: A new model system for malaria research. Cellular Microbiology 2014; 16: 612-20.
18. Barber BE, Rajahram GS, Grigg MJ, William T and Anstey NM: World Malaria Report: time to acknowledge knowlesi malaria. Malaria Journal 2017; 16: 13-15.
19. Brasil P, Zalis MG, de Pina-Costa A, Siqueira AM, Júnior CB, Silva S, Areas ALL, Pelajo-Machado M, de Alvarenga DAM, da Silva Santelli ACF, Albuquerque HG, Cravo P, Santos de Abreu FV, Peterka CL, Zanini GM, Suárez Mutis MC, Pissinatti A, Lourenço-de-Oliveira R, de Brito CFA, de Fátima Ferreira-da-Cruz M, Culleton R and Daniel-Ribeiro CT: Outbreak of human malaria caused by Plasmodium simium in the Atlantic Forest in Rio de Janeiro: A molecular epidemiological investigation. The Lancet Global Health 2017; 5: e1038-46.
20. Rajahram GS, Barber BE, William T, Grigg MJ, Menom J, Yeo TW and Anstey: Falling Plasmodium knowlesi malaria death rate among adults despite rising incidence, Sabah, Malaysia, 2010 - 2014. Emerging Infectious Diseases 2016; 22: 41-48.
21. Barber BE, Grigg MJ, Piera KA, William T, Cooper DJ, Plewes K, Dondorp AM, Yeo TW and Anstey NM: Intravascular haemolysis in severe Plasmodium knowlesi malaria: association with endothelial activation, micro-vascular dysfunction and acute kidney injury. Emerging Microbes and Infections 2018; 7: 106.
22. Chong SE, Mohamad Zaini RH, Suraiya S, Lee KT and Lim JA: The dangers of accepting a single diagnosis: case report of concurrent Plasmodium knowlesi malaria and dengue infection. Malaria Journal 2017; 16: 1-8.
23. Amir A, Russell B, Liew JWK, Moon RW, Fong MY, Vythilingam I, Subramaniam V, Snounou G and Lau YL: Invasion characteristics of a knowlesi line newly isolated from a human. Scientific Reports 2016; 6: 1-8.
24. Benavente ED, de Sessions PF, Moon RW, Grainger M, Holder AA, Blackman MJ, Roper C, Drakeley CJ, Pain A, Sutherland CJ, Hibberd ML, Campino S and Clark TG: A reference genome and methylome for the knowlesi A1-H.1 line. International J for Parasitology 2017; 48: 191-96.
25. Moon RW, Hall J, Rangkuti F, Ho YS, Almond N, Mitchell GH, Pain A, Holder AA and Blackman MJ: Adaptation of the genetically tractable malaria pathogen knowlesi to continuous culture in human erythrocytes. Proceedings of the National Academy of Sciences of the United States of America 2013; 110: 531-36.
26. Noulin F, Manesia JK, Rosanas-Urgell A, Erhart A, Borlon C, Abbeele JVD, d'Alessandro U and Verfaillie CM: Hematopoietic stem/progenitor cell sources to generate reticulocytes for Plasmodium vivax PloS One 2014; 9: e112496.
27. Ball EG, Anfinsen CB, Geiman QM, McKee RW and Ormsbee RA: In-vitro growth and multiplication of the malaria parasite. Plasmodium knowlesi. Science 1945; 101: 542-44.
28. Noulin F: Review malaria modeling: In-vitro stem cells in-vivo models. World J of Stem Cells 2016; 8:88-100.
29. Kocken CHM, Ozwara H, van der Wel A, Beetsma AL, Mwenda JM and Thomas AW: Plasmodium knowlesi provides a rapid in-vitro and in-vivo transfection system that enables double-crossover gene knockout studies. Infection and Immunity 2002; 70: 655-60.
30. Kumar AA, Lim C, Moreno Y, Mace CR, Syed A, Van Tyne D, Wirth DF, Duraisingh MT and Whitesides GM: Enrichment of reticulocytes from whole blood using aqueous multiphase systems of polymers. American Journal of Hematology 2015; 90: 31-36.
31. Pasini EM, Zeeman AM, Voorberg-Van Der Wel A and Kocken CHM: Plasmodium knowlesi: a relevant, versatile experimental malaria model. Parasitology 2018; 45: 56-70.
32. Antony HA and Parija SC: Anti-malarial drug resistance: An overview. Tropical Parasitology 2016; 6: 30-41.
33. Chitnis CE: Identification of the erythrocyte binding domains of Plasmodium vivax and Plasmodium knowlesi proteins involved in erythrocyte invasion. Journal of Experimental Medicine 1994; 180: 497-06.
34. Noulin F, Borlon C, van den Eede P, Boel L, Verfaillie CM, D’Alessandro U and Erhart A: Cryopreserved reticulocytes derived from hematopoietic stem cells can be invaded by cryopreserved Plasmodium vivax isolates. Plos One 2012; 7: 1-8.
35. Muh F, Lee SK, Hoque MR, Han JH, Park JH, Firdaus ER, Moon RW, Lau YL and Han ET: In-vitro invasion inhibition assay using antibodies against Plasmodium knowlesi Duffy binding protein alpha and apical membrane antigen protein 1 in human erythrocyte-adapted knowlesi A1-H.1 strain. Malaria Journal 2018; 17: 272.
36. Lim H, Hanssen E, DeSimone TM, Moreno Y, Junker K, Bei A, Brugnara C, Buckee CO and Duraisingh MT: Expansion of host cellular niche can drive adaptation of a zoonotic malaria parasite to humans. Nature Commu-nication 2013; 4: 1638.
37. Pain A, Böhme U, Berry AE, Mungall K, Finn RD, Jackson AP, Mourier T, Mistry J, Pasini EM, Aslett MA, Balasubrammaniam S, Borgwardt K, Brooks K, Carret C, Carver TJ, Cherevach I, Chillingworth T, Clark TG, Galinski MR, Hall N, Harper D, Harris D, Hauser H, Ivens A, Janssen CS, Keane T, Larke N, Lapp S, Marti M, Moule S, Meyer IM, Ormond D, Peters N, Sanders M, Sanders S, Sargeant TJ, Simmonds M, Smith F, Squares R, Thurston S, Tivey AR, Walker D, White B, Zuiderwijk E, Churcher C, Quail MA, Cowman AF, Turner CM, Rajandream MA, Kocken CH, Thomas AW, Newbold CI, Barrell BG and Berriman, M: The genome of the simian and human malaria parasite Plasmodium knowlesi. Nature 2008; 455: 799-03.
38. Malleret B, Li A, Zhang R, Tan KSW, Suwanarusk R, Claser C, Cho JS, Koh EGL, Chu CS, Pukrittayakamee S, Ng ML, Ginhoux F, Ng LG, Lim CT, Nosten F, Snounou G, Rénia L and Russel B: Plasmodium vivax: restricted tropism and rapid remodeling of CD71-positive reticulo-cytes. Blood 2015; 125: 1314-24.
39. Panichakul T, Sattabongkot J, Chotivanich K, Sirichaisin-thop J, Cui L and Udomsangpetch R: Production of erythropoietic cells in-vitro for continuous culture of vivax. International J for Parasitology 2007; 37: 1551-57.
40. Fernandez-Becerra C, Lelievre J, Ferrer M, Anton N, Thomson R, Peligero C, Almela MJ, Lacerda MVG, Herreros E and del Portillo HA: Red blood cells derived from peripheral blood and bone marrow CD34⁺ human hematopoietic stem cells are permissive to Plasmodium parasites infection. Memorias Do Instituto Oswaldo Cruz 2013; 108: 801-03.
41. Giarratana MC, Kobari L, Lapillonne H, Chalmers D, Kiger L, Cynober T, Douay L Ex-vivo: generation of fully mature human red blood cells from hematopoietic stem cells. Nature Biotechnology 2005; 23: 69-74.
42. Locono ML, Russo E, Anzalone R, Baiamonte E, Alberti G, Gerbino A, Maggio A, Rocca GL and Acuto S: Wharton’s jelly mesenchymal stromal cells support the expansion of cord blood-derived CD34⁺ cells mimicking a hematopoietic niche in a direct cell-cell contact culture system. Cell Transplantation 2018; 27: 117-29.
43. Douay L and Giarratana MC: Ex-vivo Generation of human red blood cells: A new advance in stem cell engineering. Humana Press, New York, Edition I, Vol. 482, 2009: 127-140.
44. Lau SX, Leong YY, Ng WH, Ng AWP, Ismail IS, Yusoff NM, Ramasamy R and Tan JJ: Human mesenchymal stem cells promote CD34⁺ hematopoietic stem cell proliferation with preserved red blood cell differentiation capacity. Cellular Biology International 2017; 41: 697-704.
45. Kumar PS, Chandrasekhar C, Srikanth L, Sunitha MM and Sarma PVGK: In-vitro differentiation and characterization of human hematopoietic CD34⁺ stem cells into erythrocytes. Journal of Stem Cells 2017; 12: 63-70.
46. Malleret B, Xu F, Mohandas N, Suwanarusk R, Chu C, Leite JA, Low K, Turner C, Sriprawat K, Zhang R, Bertrand O, Colin Y, Costa FTM, Ong CN, Ng ML, Lim CT, Nosten F, Rénia L and Russell B: Significant biochemical, biophysical and metabolic diversity in circulating human cord blood reticulocytes. Plos One 2013; 8: e76062.
47. Riley RS, Ben-Ezra JM, Goel R and Tidwell A: Reticulocytes and reticulocyte enumeration. Journal of Clinical Laboratory Analysis 2001; 15: 267-294.
48. Furuya T, Sá JM, Chitnis CE, Wellems TE and Stedman TT: Reticulocytes from cryopreserved erythroblasts support Plasmodium vivax infection in-vitro. Parasitology International 2014; 63: 278-284.
49. Tachibana S, Sullivan SA, Kawai S, Nakamura S, Kim HR, Goto N, Arisue N, Palacpac NM, Honma H, Yagi M, Tougan T, Katakai Y, Kaneko O, Mita T, Kita K, Yasutomi Y, Sutton PL, Shakhbatyan R, Horii T, Yasunaga T, Barnwell JW, Escalante AA, Carlton JM and Tanabe K: Plasmodium cynomolgi genome sequences provide insight into Plasmodium vivax and the monkey malaria clade. Nature Genetics 2012; 44: 1051-1055.
50. Lapp SA, Mok S, Zhu L, Wu H, Preiser PR, Bozdech Z and Galinski MR: Plasmodium knowlesi gene expression differs in ex-vivo compared to in-vitro blood-stage cultures. Malaria Journal 2015; 14: 110.
51. Moreno-Pérez DA, Ruíz JA and Patarroyo MA: Reticulocytes: Plasmodium vivax target cells. Biology of the Cell 2013; 105: 251-260.
52. Lim KL, Amir A, Lau YL and Fong MY: The Duffy binding protein (PkDBPαII) of Plasmodium knowlesi from Peninsular Malaysia and Malaysian Borneo show different binding activity level to human erythrocytes. Malaria Journal 2017; 16: 331.
53. Karnieli O: Stem cell manufacturing. Elsevier, Netherlands, Edition I, 2016: 141-60.
54. Borlon C, Russell B, Sriprawat K, Suwanarusk R, Erhart A, Renia L, Nosten F and D’Alessandro U: Cryopreserved Plasmodium vivax and cord blood reticulocytes can be used for invasion and short term culture. International Journal for Parasitology 2012; 42: 155-60.
55. Patrapuvich R, Lerdpanyangam K, Jenwithisuk R, Rungin S, Boonhok R, Duangmanee A, Yimamnuaychok N and Sattabongkot J: Viability and infectivity of cryopreserved Plasmodium vivax Southeast Asian Journal of Tropical Medicine and Public Health 2016; 47: 171.
56. Russell B, Suwanarusk R, Costa FTM, Chu CS, Rijken MJ, Sriprawat K, Warter L, Koh EGL, Malleret B, Colin Y, Bertrand O, Adams JH, Alessandro UD, Snounou G, Nosten F and Re L: A reliable ex-vivo invasion assay of human reticulocytes by vivax. Blood 2011; 118: 74-82.
57. Moon RW, Sharaf H, Hastings CH, Ho YS, Nair MB, Rchiad Z, Knuepfer E, Ramaprasad A, Mohring F, Amir A, Yusuf NA, Hall J, Almond N, Lau YL, Pain A, Blackman MJ and Holder AA: Normocyte-binding protein required for human erythrocyte invasion by the zoonotic malaria parasite Plasmodium knowlesi. Proceedings of the National Academy of Sciences of the United States of America 2016; 113: 7231-36.
58. Hadley TJ, Klotz FW and Miller LH: Invasion of erythrocytes by malaria parasites: a cellular and molecular overview. Annual Rev of Microbiology 1986; 40: 451-77.
59. Han JH, Lee SK, Wang B, Muh F, Nyunt MH, Na S, Ha KS, Hong SH, Park WS, Sattabongkot J, Tsuboi T and Han ET: Identification of a reticulocyte-specific binding domain of Plasmodium vivax reticulocyte-binding protein 1 that is homologous to the PfRh4 erythrocyte-binding domain. Scientific Reports 2016; 6: 26993.
60. Semenya AA, Tran TM, Meyer EV, Barnwell JW and Galinski MR: Two functional reticulocyte binding-like (RBL) invasion ligands of zoonotic Plasmodium knowlesi exhibit differential adhesion to the monkey and human erythrocytes. Malaria Journal 2012; 11: 112.
61. Ahmed MA, Fong MY, Lau YL and Yusof R: Clustering and genetic differentiation of the normocyte binding protein (nbpxa) of Plasmodium knowlesi clinical isolates from Peninsular Malaysia and Malaysia Borneo. Malaria Journal 2016; 15: 241.
62. Noulin F, Borlon C, Van Den Abbeele J, D’Alessandro U and Erhart A: 1912-2012: a century of research on Plasmodium vivax in-vitro Trends in Parasitology 2013; 29: 286-294.
63. Galinski MR, Medina CC, Ingravallo P, and Barnwell JW: A reticulocyte-binding protein complex of Plasmodium vivax Cell 1992; 69: 1213-26.
64. Carlton JM, Adams JH, Silva JC, Bidwell SL, Lorenzi H, Caler E, Crabtree J, Angiuoli SV, Merino EF, Amedeo P, Cheng Q, Coulson RM, Crabb BS, Del Portillo HA, Essien K, Feldblyum TV, Fernandez-Becerra C, Gilson PR, Gueye AH, Guo X, Kang'a S, Kooij TW, Korsinczky M, Meyer EV, Nene V, Paulsen I, White O, Ralph SA, Ren Q, Sargeant TJ, Salzberg SL, Stoeckert CJ, Sullivan SA, Yamamoto MM, Hoffman SL, Wortman JR, Gardner MJ, Galinski MR, Barnwell JW and Fraser-Liggett CM: Comparative genomics of the neglected human malaria parasite Plasmodium vivax. Nature 2008; 455: 757-63.
65. Kocken CHM, Zeeman A-M, Voorberg-van der Wel A and Thomas AW: Transgenic Plasmodium knowlesi: relieving a bottleneck in malaria research? Trends in Parasitology 2009; 25: 370-74.
66. Gilson PR and Crabb BS: Morphology and kinetics of the three distinct phases of red blood cell invasion by Plasmodium falciparum International Journal of Parasitology 2009; 39: 91-96.
67. Riglar DT, Richard D, Wilson DW, Boyle MJ, Dekiwadia C, Turnbull L, Angrisano F, Marapana DS, Rogers KL, Whitchurch CB, Beeson JG, Cowman AF, Ralph SA and Baum J: Super-resolution dissection of coordinated events during malaria parasite invasion of the human erythrocyte. Cell Host & Microbe 2011; 9: 9-20.
68. Egan ES, Jiang RH, Moechtar MA, Barteneva NS, Weekes MP, Nobre LV, Gygi SP, Paulo JA, Frantzreb C, Tani Y, Takahashi J, Watanabe S, Goldberg J, Paul AS, Brugnara C, Root DE, Wiegand RC, Doench JG and Duraisingh MT: A forward genetic screen identifies erythrocyte CD55 as essential for Plasmodium falciparum Science 2015; 348: 711-14.
69. Armstrong CM and Goldberg DE: An FKBP destabilization domain modulates protein levels in falciparum. Nature Methods 2007; 4: 1007-09.
70. Josling GA, Petter M, Oehring SC, Gupta AP, Dietz O, Wilson DW, Schubert T, Längst G, Gilson PR, Crabb BS, Moes S, Jenoe P, Lim SW, Brown GV, Bozdech Z, Voss TS and Duffy MF: A Plasmodium knowlesi bromodomain protein regulates invasion gene expression. Cell Host and Microbe 2015; 17: 741-51.
71. Collins CR, Das S, Wong EH, Andenmatten N, Stallmach R, Hackett F, Herman JP, Müller S, Meissner M and Blackman MJ: Robust inducible cre-recombinase activity in the human malaria parasite falciparum enables efficient gene deletion within a single asexual erythrocytic growth cycle. Molecular Microbiology 2013; 88: 687-01.
72. Christian M, Cermak T, Doyle EL, Schmidt C, Zhang F, Hummel A, Bogdanove AJ and Voytas DF: Targeting DNA double-strand breaks with TAL effector nucleases. Genetics 2010; 186: 757-61.
73. Knuepfer E, Napiorkowska M, van Ooij C and Holder AA: Generating conditional gene knockouts in Plasmodium - a toolkit to produce stable DiCre recombinase-expressing parasite line using CRISPR/Cas9. Scientific Reports 2017; 7: 3881.
74. Moraes Barros RR, Straimer J, Sa JM, Salzman RE, Melendez-Muniz VA, Mu J, Fidock DA and Wellems TE: Editing the Plasmodium vivax genome, using zinc-finger nucleases. The Journal of Infectious Diseases 2014; 211: 125-29.
75. Mueller I, Shakri AR and Chitnis CE: Development of vaccines for Plasmodium vivax Vaccine 2015; 33: 7489-95.
76. Ntumngia FB, Thomson-Luque R, Pires C and Adams JH: The role of the human Duffy antigen receptor for chemokines in malaria susceptibility: current opinions and future treatment prospects. Journal of Receptor, Ligand and Channel Research 2016; 9: 1-11.
    

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    Mohamad FS and Abu-Bakar N: Towards successful adaptation of Plasmodium knowlesi to long-term in-vitro culture in human erythrocytes. Int J Pharm Sci & Res 2019; 10(6): 2663-69. doi: 10.13040/IJPSR.0975-8232.10(6).2663-69.

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