Loading

JSM Allergy and Asthma

SCID Mouse-Human Lung Xenograft Models for Studying Viral Infection and Pathogenesis

Review Article | Open Access Volume 5 | Issue 1 |

  • 1. Department of Microbiology, Biochemistry and Molecular Genetics, The State University of New Jersey, USA
  • 2. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Xiamen University, China
+ Show More - Show Less
Corresponding Authors
Zhu H, Department of Microbiology, Biochemistry and Molecular Genetics, New Jersey Medical School, Rutgers, The State University of New Jersey, USA, Email: zhuhu@njms.rutgers.edu
KEYWORDS

SCID-hu mouse model; Lung xenograft; Human cytomegalovirus (HCMV); Varicella-zoster virus (VZV); Nipah virus (NiV

CITATION

Zeng M, Jaijyan DK, Wang W, Zhu H (2021) SCID Mouse-Human Lung Xenograft Models for Studying Viral Infection and Pathogenesis. JSM Allergy Asthma 5(1): 1027.

ABBREVIATIONS

HCMV: human cytomegalovirus; HZ: Herpes Zoster; FDA: Food and Drug Administration; NiV: Nipah Virus; VZV: Varicella- Zoster Virus; MERS-CoV: Middle East Respiratory Syndrome Coronavirus; ZIKV: Zika Virus; RSV: Respiratory Syncytial Virus; SCID: Severe Combined Immunodeficiency; rOka: recombinant pOka VZV strain

INTRODUCTION

Many viruses exclusively infect humans, which hampers in vivo studies of their replication, tissue tropisms, and pathogenesis. To address this limitation, humanized severe combined immunodeficiency (SCID-hu) mouse models, carrying biologically relevant human tissues or cells, have been extensively used to reproduce human disease phenotypes caused by viral infection [1]. The purpose of the SCID-hu mouse models varies depending on the type of tissue or cell  transplants it receives, which most commonly include human liver, thymus, hematopoietic stem cells, skin, dorsal root ganglion, and lung [1]. Here we review recent progress in the application of SCID mousehuman lung xenograft models, or SCID-hu lung mouse models for virus research, as well as insights into the pathogenesis of virusinduced lung diseases gained from these useful tools.

Creation of the SCID-hu lung mouse model

An ethical statement is critical when performing research on human fetal tissues. The National Institute of Health (NIH) has a regulatory process for obtaining and using human fetal tissues for research. For the establishment of SCID-hu lung
mouse models, human fetal lung tissues can be obtained from companies like Advanced Bioscience Resource (ABR), Inc., which is a non-profit tissue procurement organization that provides human fetal tissues to requesting scientific investigators? C.B- 17 SCID mice, which are homozygous for the Prkdcscid mutation and lack both T and B cells [2], are typically used for the tissue engraftment. Human fetal lung tissues are dissected into 2-8 mm size fragments under sterile conditions before being implanted under the flank skin or the kidney capsule. After 1-2 months, the lung xenografts will expand, develop mature structures closely resembling normal human lung, and can be surgically exposed for virus inoculation. The SCID-hu lung mouse model has been used to study lung infection of various viruses, including varicella-zoster virus (VZV), human cytomegalovirus (HCMV) and Nipah virus (NiV) (see below). By using this model, both viral
factors and host factors that determine viral lung infection can be analyzed in a microenvironment similar to normal human lung tissue in vivo.

The SCID-hu lung mouse model for VZV infection

VZV, also known as human herpesvirus-3 (HHV-3), is a human herpesvirus of the α?herpesvirus family. The primary infection of VZV causes chickenpox and the virus will establish latency within the neurons of the cranial nerve and dorsal root ganglia. Because of this latency, immune deterioration through factors such as age and medical conditions can cause VZV to become active again as herpes zoster (HZ), or shingles [3]. Another serious complication from VZV is varicella pneumonia, which can cause severe respiratory failure in adults and immunocompromised individuals. Over the years, VZV has mainly been studied in human cell cultures since the virus cannot infect standard animal models. The usage of the SCID-hu mouse models with implants of human skin, T cells, lung and dorsal root ganglion allow for studying VZV infection, tissue tropisms and pathogenesis within various human tissue microenvironments in vivo [4-7].

In a study of VZV in SCID-hu mice, the mice were engrafted with human fetal lung tissues. The implanted lung xenografts were then injected with the cell-free virus of rOka, a recombinant Oka expressing firefly luciferase, or mock-infected as a control. To approximately measure viral replication, bioluminescent signals were measured once every two days for 24 days, and results showed that the rOka-infected lung xenografts displayed viral spread and replication of VZV, unlike the mock-infected xenografts. The virus actively replicated and infected both the alveolar epithelial and mesenchymal cells of the lung xenografts. This viral growth additionally resulted in the upregulation of 14 pro-inflammatory cytokines because of the lack of human immune cells in the SCID-hu model. Clusters and individual nucleocapsids, some of which were wrapped by membrane vesicles and underwent second envelopment, were also observed in the nucleoplasm of the lung cells of the rOka-infected xenografts, unlike in the mock-infected controls. However, some common traits of VZV infection in humans were not shown in the rOka-infected lung xenografts: tissue structures remained intact in the uninfected areas outside the viral lesions, no staining was observed, and no cell fusion or syncytia formation was shown. Despite this, because of its ability to replicate VZV pathogenesis in a microenvironment similar to human lung tissue, the SCID mouse-human lung xenograft model could aid in future antiviral developments and treatments for VZV-related lung diseases, as well as provide answers as to why immunocompromised individuals are more prone to severe pulmonary complications as a result of VZV infection [(6].

The SCID-hu lung mouse model for NiV infection

NiV is an emerging zoonotic virus that causes severe respiratory illness, acute lung injury, and encephalitis, which has a 92% mortality rate in humans [8]. Human-to-human transmission of NiV, as well as animal-to-human, has previously
been reported [9-11]. Typically, NiV infects endothelial cells in the lung, but there is limited research data following viral infection, due to the lack of human tissue samples. The histopathological data of NiV infected lungs obtained after necropsy shows the hemorrhage, necrosis, and inflammation of lung epithelium. NiV has been found to be able to infect and replicate to higher titers in the lungs of animal models such as the hamster, ferret, and African green monkey [10,12-15], but a human lung xenograft mouse model of NiV had not yet been established when these studies were being conducted. The exact mechanism of NiV pathogenesis in humans is still unknown, and there is an urgent need to study the molecular mechanism of NiV pathogenesis in order to develop anti-viral drugs and vaccines. It has been reported that the respiratory epithelium plays a major role in early viral infection; therefore, a lung xenograft mouse model for NiV is critical to study viral pathogenesis in the lung and to test the efficacy of antiviral drugs. A human lung xenograft mouse model has recently been developed for the study of NiV infection as a result [16]. The SCID mice (Jackson Laboratory) were transplanted with human fetal lung tissues (obtained from ABR Inc) on the dorsal muscle fascia in the dorsal subcutaneous space. This xenograft mouse model of the human lung demonstrated that following transplantation, lung tissues rapidly develop mature structures resembling those of adult lungs’, including vascular vessels, cartilage, ciliated pseudostratified columnar epitheliums, and primitive air space filled with mucus and surrounded by flat epithelium [16]. In this model, NiV was found to replicate in the respiratory epithelium of small airways and bronchi as well as mesenchymal cells. Moreover, NiV was also detected in the endothelium cells, cells that are commonly targeted by the virus. Furthermore, intraperitoneal inoculation of NiV led to the infection of human lung xenografts, suggesting hematogenous viral spread. In this mouse model, NiV was able to replicate to higher titers in human lung tissue and cause pulmonary syncytia formation after three days of post-infection. Histopathological analysis showed that NiV infection caused extensive necrosis, syncytia formation and loss of alveolar architecture in the lung xenografts. The infection stimulates a strong inflammatory response caused by an acute lung injury. This mouse model will be very helpful in unraveling the host-virus interactions and can be used for many other pathogens that cause respiratory diseases.

The SCID-hu lung mouse model for HCMV infection

HCMV, or human betaherpesvirus 5, is a large DNA virus that infects people of all ages. HCMV infects 60-70% of adults in developed countries and more than 90% of adults in developing countries. HCMV infection is usually asymptomatic
in healthy people, but immunocompromised patients and patients with organ transplant are at greater risk of infection. Moreover, HCMV is a leading cause of birth defects in newborns, affecting 1% of all births worldwide [17]. Mature children and immunocompromised patients are typically associated with life-threatening respiratory lung-related disease from HCMV infection. Studies have also shown that HCMV mainly targets the lung for infection and replication in fetuses, as well as in newborns [18]. HCMV is uniquely a human pathogen and does not infect animals [19], which brings up the need for an in vivo animal model that can be infected with HCMV. A SCID-hu mouse model with human fetal lung xenografts was generated by implanting the fetal lung tissue under the kidney capsular membranes of C.B- 17-SCID mice [20]. The clinical VR1814 strain of HCMV was then allowed to infect the lung xenograft, and results demonstrated that the virus efficiently replicated for a period of two weeks and formed large viral lesions. HCMV was found to have replicated in alveolar epithelial and mesenchymal cells, similar to congenital HCMV infection of the fetal lung. Additionally, HCMV glycoprotein B was readily detected by immunofluorescence and western blot, confirming viral infection in the lung xenografts. The anti-HCMV drug, ganciclovir and valganciclovir, treatments reduced the viral load in the lung of SCID mice, suggesting applications for antiviral drug screening. Staining in the lung xenografts confirmed viral replication in the alveolar epithelial cells, similar to natural HCMV infection. Moreover, the immunostaining infected xenografts showed that HCMV impaired the secretion of surfactant proteins from alveolar epithelial cells. This mouse model recapitulates the fetal as well as neonate lung development and represents an important tool to study HCMV, as well as other human pathogens that target the lung.

A human lung xenograft mouse model with expanded tropisms for human pathogens

Recently, a study has evaluated both lung-only humanized mice and bone marrow/liver/thymus-lung humanized mice to study lung infection of several emerging and clinically relevant human pathogens such as Middle East respiratory syndrome coronavirus (MERS-CoV), Zika virus (ZIKV), respiratory syncytial virus (RSV), and HCMV (21). The results obtained in this study clearly demonstrate that the subcutaneous implantation of human lung tissue in the backs of SCID mice resulted in a highly vascularized lung xenograft located just underneath the skin, allowing for easy accessibility and imaging [21]. This created humanized lung-only mice (LoM). The human lung tissues vascularized, persisted, and expanded as a human lung xenograft that supports the infection and replication of human pathogens, including viruses and bacteria. The lung xenografts were ectopic and not ventilated, but the xenografts still had welldefined structures that are characteristic of the human lung, including ciliated epithelium, airways, associated blood vessels, cartilage, and alveolar structures. The ex vivo culture of lung xenografts has the ability to produce human chemokines and cytokines, suggesting an ability to function similarly to normal human lungs. The authors of this study used immunostaining and histopathological analysis to show that LoM can be infected by a diverse set of pathogens including HCMV, MERS-CoV, ZIKV), RSV, and mycobacteria. Specifically, HCMV TB40/E, a clinical HCMV strain, was administered, and HCMV DNA and proteins were detected in the infected lung xenografts, demonstrating active viral replication. Ganciclovir treatment of LoM infected with HCMV reduced the viral load in the human lung xenografts.

The LoM mouse model can be used for virus replication and pathogenesis studies. To understand the role of host immunity in virus pathogenesis, a humanized BLT-L mouse model was also generated by implanting human lung tissue in BLT mice and was named the BLT-lung (BLT-L) model. The BLT-L mouse was created by implanting autologous human liver and thymus tissues under the kidney capsule and human lung tissue under the skin of the same preconditioned irradiated mouse, followed by bone marrow transplantation with autologous hematopoietic stem cells [21]. Therefore, a BLT-L mouse model consists of human liver and thymus tissues under the kidney capsule, along with human bone marrow tissue and human lung tissue. Therefore, the BLT-L model will have a systemic autologous human innate and adaptive immune response. The BLT-L mice also consist of human mesenchymal, epithelial, and endothelial cells. When infected with HCMV, the model shows viral gene expression and generates specific B and T cells response against HCMV infection. BLT-L mouse can be infected with a diverse set of respiratory pathogens including RSV, ZIKV, MERS-CoV, mycobacterium, HCMV, and other providing an opportunity to study their replication, pathogenesis, and host immune response activation in parallel. BLT-L mice recapitulate viral infection in humans with similar kinetics and replication, providing a valuable tool to study virus pathogenesis as well as host immune response [21].

DISCUSSION

It is often difficult to perform research on human-specific viruses because of their inability to infect standard animal models. Human-specific viruses, such as VZV, HCMV and HIV, only infect humans and lack animal models. This makes studies of
viral replication and pathogenesis in vivo and preclinical trials of antiviral compounds extremely difficult. Therefore, a humanized mouse model is urgently needed.

The genetic mutation that SCID mice carry enables them to accept xenografts of human tissues and organs, creating humanized mice. One type of humanized mice is the SCID-hu lung mouse, which is created by engrafting human fetal lung tissues underneath the kidney capsules or back of C.B-17 SCID mice. Within eight weeks, the mice develop mature lung structures that function similarly to normal human lung tissues. The model can be applied in various in vivo studies of viruses that target the lung, including VZV, HCMV and NiV. These viruses are able to infect the lung xenografts of the SCID-hu mice, and immune responses can be observed within the mice over a period of time. After infection, the models display viral responses similar to that of humans’, including effective viral replication in alveolar epithelial and mesenchymal cells, as well as inflammatory cytokine production. In a study of VZV infection in SCID-hu mice, it was found that viral growth did not cease in response to the pro-inflammatory response; in fact, it continued for a longer period of time until the fetal lung tissues from the implantation sites completely collapsed5. Furthermore, anti-viral treatments and their effects can be tested in SCID-hu mice, allowing for the developments of novel drug targets. The immunostaining and histopathological analysis of infected lung xenograft shows that viruses can replicate efficiently and cause syncytia formation and loss of alveolar structures, recapitulating natural infection. It has also been demonstrated that active viral replication leads to the robust necrosis of infected cells in the lung xenograft19. This evidence strongly suggests that a SCID-hu model infection with diverse set of human pathogens recapitulate the natural infection in terms of pathogenesis, replication, inflammatory response and generate similar histopathological data as with human infection.

However, there are several limitations to this model. SCID-hu models lack human immune cells and does not have the adaptive immunity needed for precise studies on host immune response to viral infection. Moreover, a SCID mouse model may not be suitable for studying viral latency because viruses such as VZV establish latency in neurons and HCMV in lymphocytes. Most of the time, active viral replication leads to the infection of other organs such as the liver, kidney, and brain, as in case of HCMV, fetal brain, in the case of ZIKV, which leads to microcephaly; therefore, the SCID model may not be used for complete pathogenesis study of a virus. To overcome this limitation to an extent, a novel humanized
SCID mouse model, BLT-lung mouse model (BLT-L), has been developed. The BLT-L model contains up to 40 cell types, including non-hematopoietic cells, and it contains xenografts from the human lung, thymus, liver and bone marrow. This
allows for the model to have a systemic autologous human innate and adaptive immune response, permitting studies of immune responses to viral infections in SCID mice. BLT-L mice have also been used to study HCMV pathogenesis, where specific B and T cell reactions could be generated in response.

With the usage of SCID-hu mouse models, disease pathology can be further studied without putting human patients at risk. The SCID-hu lung mouse model will help identify viral or host factors that cause the development of diseases caused by lung-related viruses, including RSV, MERS-CoV, HCMV, and NiV. Furthermore, the addition of the BLT-L mouse model allows for the number of human pathogens that can be studied in vivo to be substantially increased. Because of its ability to be generated in large numbers from small tissue samples, the SCID-hu lung model is also able to meet the demand for research on human-specific viruses and their pathogeneses, increasing its usability and relevance in the field. In the future, these humanized mouse models may be the key to develop novel antiviral compounds and treatments for human autoimmune diseases involving the lungs.

REFERENCES

1. Lai F, Chen QF. Humanized Mouse Models for the Study of Infection and Pathogenesis of Human Viruses. Viruses-Basel. 2018; 10: 643.

2. Huang P, Westmoreland SV, Jain RK, Fukumura D. Spontaneous nonthymic tumors in SCID mice. Comp Med. 2011; 61: 227-34.

3. Pergam SA, Limaye AP, Practice ASTIDCo. Varicella zoster virus (VZV) in solid organ transplant recipients. Am J Transplant. 2009; 9: S108-15.

4. Selariu A, Cheng T, Tang QY, Silver B, Yang LW, Liu C, et al. ORF7 of Varicella-Zoster Virus Is a Neurotropic Factor. J Virol. 2012; 86: 8614-24.

5. Wang W, Wang X, Yang LW, Fu WK, Pan DQ, Liu J, et al. Modulation of host CD59 expression by varicella-zoster virus in human xenografts in vivo. Virology. 2016; 491: 96-105.

6. Wang W, Pan D, Fu W, Cai L, Ye J, Liu J, et al. A SCID mouse-human lung xenograft model of varicella-zoster virus infection. Antiviral Res. 2017; 146: 45-53.

7. Mahalingam R, Gershon A, Gershon M, Cohen JI, Arvin A, Zerboni L, et al. Current In Vivo Models of Varicella-Zoster Virus Neurotropism.Viruses. 2019; 11: 502.

8. Rockx B, Winegar R, Freiberg AN. Recent progress in henipavirus research: molecular biology, genetic diversity, animal models. Antiviral Res. 2012; 95: 135-49.

9. Gurley ES, Montgomery JM, Hossain MJ, Bell M, Azad AK, Islam MR, et al. Person-to-person transmission of Nipah virus in a Bangladeshi community. Emerg Infect Dis. 2007; 13: 1031-7.

10. Hossain MJ, Gurley ES, Montgomery JM, Bell M, Carroll DS, Hsu VP, et al. Clinical presentation of nipah virus infection in Bangladesh. Clin Infect Dis. 2008; 46: 977-84.

11. Escaffre O, Borisevich V, Rockx B. Pathogenesis of Hendra and Nipah virus infection in humans. J Infect Dev Ctries. 2013; 7: 308-11

12. Bossart KN, Rockx B, Feldmann F, Brining D, Scott D, LaCasse R, et al. A Hendra virus G glycoprotein subunit vaccine protects African green monkeys from Nipah virus challenge. Sci Transl Med. 2012; 4: 146ra07.

13. Bossart KN, Zhu Z, Middleton D, Klippel J, Crameri G, Bingham J, et al. A neutralizing human monoclonal antibody protects against lethal disease in a new ferret model of acute nipah virus infection. PLoS Pathog. 2009; 5: e1000642.

14. Geisbert TW, Daddario-DiCaprio KM, Hickey AC, Smith MA, Chan YP, Wang LF, et al. Development of an acute and highly pathogenic nonhuman primate model of Nipah virus infection. PLoS One. 2010; 5: e10690.

15. Wong KT, Grosjean I, Brisson C, Blanquier B, Fevre-Montange M, Bernard A, et al. A golden hamster model for human acute Nipah virus infection. Am J Pathol. 2003; 163: 2127-37.

16. Valbuena G, Halliday H, Borisevich V, Goez Y, Rockx B. A human lung xenograft mouse model of Nipah virus infection. PLoS Pathog. 2014; 10: e1004063.

17. Lazzarotto T, Blazquez-Gamero D, Delforge ML, Foulon I, Luck S, Modrow S, et al. Congenital Cytomegalovirus Infection: A Narrative Review of the Issues in Screening and Management From a Panel of European Experts. Front Pediatr. 2020; 8: 13.

18. Gabrielli L, Bonasoni MP, Lazzarotto T, Lega S, Santini D, Foschini MP, et al. Histological findings in foetuses congenitally infected by cytomegalovirus. J Clin Virol. 2009; 46: S16-21.

19. Crawford LB, Streblow DN, Hakki M, Nelson JA, Caposio P. Humanized mouse models of human cytomegalovirus infection. Curr Opin Virol. 2015; 13: 86-92.

20. Maidji E, Kosikova G, Joshi P, Stoddart CA. Impaired surfactant production by alveolar epithelial cells in a SCID-hu lung mouse model of congenital human cytomegalovirus infection. J Virol. 2012; 86:12795-805.

21. Colugnati FAB, Staras SAS, Dollard SC, Cannon MJ. Incidence of cytomegalovirus infection among the general population and pregnant women in the United States. BMC Infect Dis. 2007; 7: 71..

Zeng M, Jaijyan DK, Wang W, Zhu H (2021) SCID Mouse-Human Lung Xenograft Models for Studying Viral Infection and Pathogenesis. JSM Allergy Asthma 5(1): 1027.

Received : 12 Jan 2021
Accepted : 26 Jan 2021
Published : 28 Jan 2021
Journals
Annals of Otolaryngology and Rhinology
ISSN : 2379-948X
Launched : 2014
JSM Schizophrenia
Launched : 2016
Journal of Nausea
Launched : 2020
JSM Internal Medicine
Launched : 2016
JSM Hepatitis
Launched : 2016
JSM Oro Facial Surgeries
ISSN : 2578-3211
Launched : 2016
Journal of Human Nutrition and Food Science
ISSN : 2333-6706
Launched : 2013
JSM Regenerative Medicine and Bioengineering
ISSN : 2379-0490
Launched : 2013
JSM Spine
ISSN : 2578-3181
Launched : 2016
Archives of Palliative Care
ISSN : 2573-1165
Launched : 2016
JSM Nutritional Disorders
ISSN : 2578-3203
Launched : 2017
Annals of Neurodegenerative Disorders
ISSN : 2476-2032
Launched : 2016
Journal of Fever
ISSN : 2641-7782
Launched : 2017
JSM Bone Marrow Research
ISSN : 2578-3351
Launched : 2016
JSM Mathematics and Statistics
ISSN : 2578-3173
Launched : 2014
Journal of Autoimmunity and Research
ISSN : 2573-1173
Launched : 2014
JSM Arthritis
ISSN : 2475-9155
Launched : 2016
JSM Head and Neck Cancer-Cases and Reviews
ISSN : 2573-1610
Launched : 2016
JSM General Surgery Cases and Images
ISSN : 2573-1564
Launched : 2016
JSM Anatomy and Physiology
ISSN : 2573-1262
Launched : 2016
JSM Dental Surgery
ISSN : 2573-1548
Launched : 2016
Annals of Emergency Surgery
ISSN : 2573-1017
Launched : 2016
Annals of Mens Health and Wellness
ISSN : 2641-7707
Launched : 2017
Journal of Preventive Medicine and Health Care
ISSN : 2576-0084
Launched : 2018
Journal of Chronic Diseases and Management
ISSN : 2573-1300
Launched : 2016
Annals of Vaccines and Immunization
ISSN : 2378-9379
Launched : 2014
JSM Heart Surgery Cases and Images
ISSN : 2578-3157
Launched : 2016
Annals of Reproductive Medicine and Treatment
ISSN : 2573-1092
Launched : 2016
JSM Brain Science
ISSN : 2573-1289
Launched : 2016
JSM Biomarkers
ISSN : 2578-3815
Launched : 2014
JSM Biology
ISSN : 2475-9392
Launched : 2016
Archives of Stem Cell and Research
ISSN : 2578-3580
Launched : 2014
Annals of Clinical and Medical Microbiology
ISSN : 2578-3629
Launched : 2014
JSM Pediatric Surgery
ISSN : 2578-3149
Launched : 2017
Journal of Memory Disorder and Rehabilitation
ISSN : 2578-319X
Launched : 2016
JSM Tropical Medicine and Research
ISSN : 2578-3165
Launched : 2016
JSM Head and Face Medicine
ISSN : 2578-3793
Launched : 2016
JSM Cardiothoracic Surgery
ISSN : 2573-1297
Launched : 2016
JSM Bone and Joint Diseases
ISSN : 2578-3351
Launched : 2017
JSM Bioavailability and Bioequivalence
ISSN : 2641-7812
Launched : 2017
JSM Atherosclerosis
ISSN : 2573-1270
Launched : 2016
Journal of Genitourinary Disorders
ISSN : 2641-7790
Launched : 2017
Journal of Fractures and Sprains
ISSN : 2578-3831
Launched : 2016
Journal of Autism and Epilepsy
ISSN : 2641-7774
Launched : 2016
Annals of Marine Biology and Research
ISSN : 2573-105X
Launched : 2014
JSM Health Education & Primary Health Care
ISSN : 2578-3777
Launched : 2016
JSM Communication Disorders
ISSN : 2578-3807
Launched : 2016
Annals of Musculoskeletal Disorders
ISSN : 2578-3599
Launched : 2016
Annals of Virology and Research
ISSN : 2573-1122
Launched : 2014
JSM Renal Medicine
ISSN : 2573-1637
Launched : 2016
Journal of Muscle Health
ISSN : 2578-3823
Launched : 2016
JSM Genetics and Genomics
ISSN : 2334-1823
Launched : 2013
JSM Anxiety and Depression
ISSN : 2475-9139
Launched : 2016
Clinical Journal of Heart Diseases
ISSN : 2641-7766
Launched : 2016
Annals of Medicinal Chemistry and Research
ISSN : 2378-9336
Launched : 2014
JSM Pain and Management
ISSN : 2578-3378
Launched : 2016
JSM Women's Health
ISSN : 2578-3696
Launched : 2016
Clinical Research in HIV or AIDS
ISSN : 2374-0094
Launched : 2013
Journal of Endocrinology, Diabetes and Obesity
ISSN : 2333-6692
Launched : 2013
Journal of Substance Abuse and Alcoholism
ISSN : 2373-9363
Launched : 2013
JSM Neurosurgery and Spine
ISSN : 2373-9479
Launched : 2013
Journal of Liver and Clinical Research
ISSN : 2379-0830
Launched : 2014
Journal of Drug Design and Research
ISSN : 2379-089X
Launched : 2014
JSM Clinical Oncology and Research
ISSN : 2373-938X
Launched : 2013
JSM Bioinformatics, Genomics and Proteomics
ISSN : 2576-1102
Launched : 2014
JSM Chemistry
ISSN : 2334-1831
Launched : 2013
Journal of Trauma and Care
ISSN : 2573-1246
Launched : 2014
JSM Surgical Oncology and Research
ISSN : 2578-3688
Launched : 2016
Annals of Food Processing and Preservation
ISSN : 2573-1033
Launched : 2016
Journal of Radiology and Radiation Therapy
ISSN : 2333-7095
Launched : 2013
JSM Physical Medicine and Rehabilitation
ISSN : 2578-3572
Launched : 2016
Annals of Clinical Pathology
ISSN : 2373-9282
Launched : 2013
Annals of Cardiovascular Diseases
ISSN : 2641-7731
Launched : 2016
Journal of Behavior
ISSN : 2576-0076
Launched : 2016
Annals of Clinical and Experimental Metabolism
ISSN : 2572-2492
Launched : 2016
Clinical Research in Infectious Diseases
ISSN : 2379-0636
Launched : 2013
JSM Microbiology
ISSN : 2333-6455
Launched : 2013
Journal of Urology and Research
ISSN : 2379-951X
Launched : 2014
Journal of Family Medicine and Community Health
ISSN : 2379-0547
Launched : 2013
Annals of Pregnancy and Care
ISSN : 2578-336X
Launched : 2017
JSM Cell and Developmental Biology
ISSN : 2379-061X
Launched : 2013
Annals of Aquaculture and Research
ISSN : 2379-0881
Launched : 2014
Clinical Research in Pulmonology
ISSN : 2333-6625
Launched : 2013
Journal of Immunology and Clinical Research
ISSN : 2333-6714
Launched : 2013
Annals of Forensic Research and Analysis
ISSN : 2378-9476
Launched : 2014
JSM Biochemistry and Molecular Biology
ISSN : 2333-7109
Launched : 2013
Annals of Breast Cancer Research
ISSN : 2641-7685
Launched : 2016
Annals of Gerontology and Geriatric Research
ISSN : 2378-9409
Launched : 2014
Journal of Sleep Medicine and Disorders
ISSN : 2379-0822
Launched : 2014
JSM Burns and Trauma
ISSN : 2475-9406
Launched : 2016
Chemical Engineering and Process Techniques
ISSN : 2333-6633
Launched : 2013
Annals of Clinical Cytology and Pathology
ISSN : 2475-9430
Launched : 2014
Journal of Neurological Disorders and Stroke
ISSN : 2334-2307
Launched : 2013
Annals of Sports Medicine and Research
ISSN : 2379-0571
Launched : 2014
JSM Sexual Medicine
ISSN : 2578-3718
Launched : 2016
Annals of Vascular Medicine and Research
ISSN : 2378-9344
Launched : 2014
JSM Biotechnology and Biomedical Engineering
ISSN : 2333-7117
Launched : 2013
Journal of Hematology and Transfusion
ISSN : 2333-6684
Launched : 2013
JSM Environmental Science and Ecology
ISSN : 2333-7141
Launched : 2013
Journal of Cardiology and Clinical Research
ISSN : 2333-6676
Launched : 2013
JSM Nanotechnology and Nanomedicine
ISSN : 2334-1815
Launched : 2013
Journal of Ear, Nose and Throat Disorders
ISSN : 2475-9473
Launched : 2016
JSM Ophthalmology
ISSN : 2333-6447
Launched : 2013
Journal of Pharmacology and Clinical Toxicology
ISSN : 2333-7079
Launched : 2013
Annals of Psychiatry and Mental Health
ISSN : 2374-0124
Launched : 2013
Medical Journal of Obstetrics and Gynecology
ISSN : 2333-6439
Launched : 2013
Annals of Pediatrics and Child Health
ISSN : 2373-9312
Launched : 2013
JSM Clinical Pharmaceutics
ISSN : 2379-9498
Launched : 2014
JSM Foot and Ankle
ISSN : 2475-9112
Launched : 2016
JSM Alzheimer's Disease and Related Dementia
ISSN : 2378-9565
Launched : 2014
Journal of Addiction Medicine and Therapy
ISSN : 2333-665X
Launched : 2013
Journal of Veterinary Medicine and Research
ISSN : 2378-931X
Launched : 2013
Annals of Public Health and Research
ISSN : 2378-9328
Launched : 2014
Annals of Orthopedics and Rheumatology
ISSN : 2373-9290
Launched : 2013
Journal of Clinical Nephrology and Research
ISSN : 2379-0652
Launched : 2014
Annals of Community Medicine and Practice
ISSN : 2475-9465
Launched : 2014
Annals of Biometrics and Biostatistics
ISSN : 2374-0116
Launched : 2013
JSM Clinical Case Reports
ISSN : 2373-9819
Launched : 2013
Journal of Cancer Biology and Research
ISSN : 2373-9436
Launched : 2013
Journal of Surgery and Transplantation Science
ISSN : 2379-0911
Launched : 2013
Journal of Dermatology and Clinical Research
ISSN : 2373-9371
Launched : 2013
JSM Gastroenterology and Hepatology
ISSN : 2373-9487
Launched : 2013
Annals of Nursing and Practice
ISSN : 2379-9501
Launched : 2014
JSM Dentistry
ISSN : 2333-7133
Launched : 2013
Author Information X