Lymphocytic Choriomeningitis Virus (LCMV): Current Status and Future Directions for Clinical and Molecular Diagnostic Techniques
Keywords:
Diagnosis, Chronic infection, LCMV, CNSAbstract
Lymphocytic choriomeningitis virus is an RNA virus that is often overlooked despite the potential to cause severe illness. It is a significant cause of viral meningitis, particularly in specific clinical situations. LCMV is transmitted to humans when they come into contact with the secretions of infected mice, and its strong neurotropism primarily results in neurological symptoms. The most vulnerable populations are fetuses and immunosuppressed individuals. LCMV infection acquired through various means can manifest with a wide range of clinical symptoms, varying from being asymptomatic to severe manifestations.
Additionally, in cases where individuals are affected by this viral infection, it can result in fatal central nervous system disorders. Specifically, in pregnant women, intrauterine LCMV infection has been observed to lead to fetal or neonatal mortality. Furthermore, it can cause chorioretinitis and hydrocephalus in infants, which not only causes significant harm but also results in long-term impairments.
Timely identification and immediate intervention are crucial in improving the prognosis, especially among high-risk groups and regions where the infection is prevalent. Failure to promptly diagnose the condition can lead to significant mortality rates and leave survivors with long-term neurological complications. Consequently, it is imperative to utilize the most appropriate laboratory diagnostic approach, considering the patient's clinical symptoms, exposure history to the virus, and the prevalence of the pathogen in the area, to facilitate accurate clinical detection. This comprehensive review encompasses various diagnostic methodologies employed in managing LCMV, encompassing clinical manifestations, diagnosis, treatment, and potential complications associated with viral infections affecting the central nervous system.
References
Chakrabartty I, Khan M, Mahanta S, Chopra H, Dhawan M, Choudhary OP et al. Comparative overview of emerging RNA viruses: Epidemiology, pathogenesis, diagnosis and current treatment. Ann Med Surg(Lond). 2022; 79: 103985. doi: 10.1016/j.amsu.2022.103985.
Pencole L, Sibiude J, Weingertner AS, Mandelbrot L, Vauloup?Fellous C, Picone O. Congenital lymphocytic choriomeningitis virus: A review. Prenatal Diagnosis. 2022; 42(8): 1059-69. doi: 10.1002/pd.6192.
Vilibic-Cavlek T, Savic V, Ferenc T, Mrzljak A, Barbic L, Bogdanic M et al. Lymphocytic Choriomeningitis-Emerging Trends of a Neglected Virus: A Narrative Review. Trop Med Infect Dis. 2021; 6(2): 88. doi: 10.3390/tropicalmed6020088.
Shafaati M, Zandi M. Monkeypox virus neurological manifestations in comparison to other orthopoxviruses. Travel Med Infect Dis. 2022; 49: 102414. doi: 10.1016/j.tmaid. 2022.102414. Epub 2022 Aug 2.
Le Govic Y, Demey B, Cassereau J, Bahn YS, Papon N. Pathogens infecting the central nervous system. PLoS Pathog. 2022; 18(2): e1010234. doi: 10.1371/journal.ppat.1010234.
Larsen PD, Chartrand SA, Tomashek KM, Hauser LG, Ksiazek TG. Hydrocephalus complicating lymphocytic choriomeningitis virus infection. Pediatr Infect Dis J. 1993; 12(6): 528-31.
Ferenc T, Vujica M, Mrzljak A, Vilibic-Cavlek T. Lymphocytic choriomeningitis virus: An under-recognized congenital teratogen. World J Clin Cases. 2022; 10(25): 8922-31.
Pal M, Gutama KP, Singh S. Lymphocytic choriomeningitis: an emerging and re-emerging Rodent-Borne viral zoonotic disease. J Adv Microbiol Res. 2022; 3(2): 01-4.
Ferenc T, Vujica M, Mrzljak A, Vilibic-Cavlek T. Lymphocytic choriomeningitis virus: An under-recognized congenital teratogen. World J Clin Cases. 2022; 10(25): 8922-31.
Tevaearai F, Moser L, Pomar L. Prenatal diagnosis of congenital lymphocytic choriomeningitis virus infection: a case report. Viruses. 2022 Nov 21; 14(11): 2586.
Azim KF, Lasker T, Akter R, Hia MM, Bhuiyan OF, Hasan M et al. Combination of highly antigenic nucleoproteins to inaugurate a cross-reactive next generation vaccine candidate against Arenaviridae family. Heliyon. 2021; 7(5): e07022. doi: 10.1016/j.heliyon.2021.e07022.
Organization WH. Managing epidemics: key facts about major deadly diseases: World Health Organization; 2018.
Liu J, Knopp KA, Rackaityte E, Wang CY, Laurie MT, Sunshine S et al. Genome-wide knockout screen identifies human sialomucin CD164 as an essential entry factor for lymphocytic choriomeningitis virus. Mbio. 2022; 13(3): e00205-22.
Khole A, Theodoropoulos NM. Viral Encephalitides Including Rabies and Lymphocytic Choriomeningitis Virus: Impact in Transplant Donors and Recipients. In: Morris MI, Kotton CN, wolfe C. (eds) Emerging Transplant Infections. Springer Cham. 2020. doi: 10.1007/978-3-030-01751-4_42-1.
Liu L, Wang P, Liu A, Zhang L, Yan L, Guo Y et al. Structure basis for allosteric regulation of lymphocytic choriomeningitis virus polymerase function by Z matrix protein. Protein Cell. 2023; 14(9): 703-7. doi: 10.1093/procel/pwad018.
Belnoue E, Vogelzang A, Nieuwenhuizen NE, Krzyzaniak MA, Darbre S, Kreutzfeldt M. Replication-deficient lymphocytic choriomeningitis virus-vectored vaccine candidate for the induction of t cell immunity against Mycobacterium tuberculosis. Int J Mol Sci. 2022; 23(5): 2700.
Olivieri NR, Othman L, Flannery DD, Gordon SM. Transmission, seroprevalence, and maternal-fetal impact of lymphocytic choriomeningitis virus. Pediatr Res. 2024; 95(2): 456-463. doi: 10.1038/s41390-023-02859-w. Epub 2023 Oct 19.
Liu Z, Li L, Wang D, Zhang L, Wang Z, Fan S et al. Molecular detection and phylogenetic analysis of Lymphatic choriomeningitis virus (LCMV) in ticks in Jilin Province, northeastern China. J Vet Med Sci. 2023; 85(3): 393-8. doi: 10.1292/jvms.22-0441. Epub 2023 Mar 9.
Vilibic-Cavlek T, Savic V, Ferenc T, Mrzljak A, Barbic L, Bogdanic M et al. Lymphocytic Choriomeningitis—emerging trends of a neglected Virus: A narrative review. Trop Med Infect Dis. 2021; 6(2): 88.
Riera L, Castillo E, Del Carmen Saavedra M, Priotto J, Sottosanti J, Polop J et al. Serological study of the lymphochoriomeningitis virus (LCMV) in an inner city of Argentina. J Med Virol. 2005; 76(2): 285-9.
Emonet S, Retornaz K, Gonzalez JP, de Lamballerie X, Charrel RN. Mouse-to-human transmission of variant lymphocytic choriomeningitis virus. Emerg Infect Dis. 2007; 13(3): 472-5.
Hotchin J, Sikora E, Kinch W, Hinman A, Woodall J. Lymphocytic choriomeningitis in a hamster colony causes infection of hospital personnel. Science. 1974; 185(4157): 1173-4.
Macneil A, Ströher U, Farnon E, Campbell S, Cannon D, Paddock CD et al. Solid organ transplant-associated lymphocytic choriomeningitis, United States, 2011. Emerg Infect Dis. 2012; 18(8): 1256-62.
Mrzljak A, Novak R, Pandak N, Tabain I, Franusic L, Barbic L et al. Emerging and neglected zoonoses in transplant population. World J Transpl. 2020; 10(3): 47.
Ansari N, Demmler-Harrison G, Coats DK, Paysse EA. Severe congenital chorioretinitis caused by congenital lymphocytic choriomeningitis virus infection. Am J Ophthalmol Case Rep. 2021; 22: 101094.
Albariño CG, Palacios G, Khristova ML, Erickson BR, Carroll SA, Comer JA et al. High diversity and ancient common ancestry of lymphocytic choriomeningitis virus. Emerg Infect Dis. 2010; 16(7): 1093-100.
Buchmeier MJ, Welsh RM, Dutko FJ, Oldstone MB. The virology and immunobiology of lymphocytic choriomeningitis virus infection. Adv Immunol. 1980; 30: 275-331.
Takagi T, Ohsawa M, Morita C, Sato H, Ohsawa K. Genomic analysis and pathogenic characteristics of lymphocytic choriomeningitis virus strains isolated in Japan. Comp Med. 2012; 62(3): 185-92.
Abdel-Hakeem MS. Viruses Teaching Immunology: Role of LCMV Model and Human Viral Infections in Immunological Discoveries. Viruses. 2019; 11(2): 106. doi: 10.3390/v11020106.
Zhou X, Ramachandran S, Mann M, Popkin DL. Role of lymphocytic choriomeningitis virus (LCMV) in understanding viral immunology: past, present and future. Viruses. 2012; 4(11): 2650-69.
Sharma K, Singhapakdi K, Maertens P. Echoencephalography of encephalopathy due to congenital lymphocytic choriomeningitis virus. J Neuroimag. 2022; 32(3): 412-9.
Delaine M, Weingertner AS, Nougairede A, Lepiller Q, Fafi-Kremer S, Favre R et al. Microcephaly Caused by Lymphocytic Choriomeningitis Virus. Emerg Infect Dis. 2017; 23(9): 1548-50.
Erdin M, Stanoeva KR, Mögling R, Korva M, Knap N, Rus KR et al. External quality assessment of orthohantavirus and lymphocytic choriomeningitis virus molecular detection and serology in Europe, 2021. Eurosurveillance. 2023; 28(40): 2300054.
Juncker-Voss M, Prosl H, Lussy H, Enzenberg U, Auer H, Lassnig H et al. Screening for antibodies against zoonotic agents among employees of the Zoological Garden of Vienna, Schönbrunn, Austria. Berl Munch Tierarztl Wochenschr. 2004; 117(9-10): 404-9.
Meritet JF, Krivine A, Lewin F, Poissonnier MH, Poizat R, Loget P et al. A case of congenital lymphocytic choriomeningitis virus (LCMV) infection revealed by hydrops fetalis. Prenat Diagn. 2009; 29(6): 626-7.
Anesi JA, Silveira FP. Arenaviruses and West Nile Virus in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transpl. 2019; 33(9): e13576.
Jamieson DJ, Kourtis AP, Bell M, Rasmussen SA. Lymphocytic choriomeningitis virus: an emerging obstetric pathogen? Am J Obstet Gynecol. 2006; 194(6): 1532-6.
Cantey JB. Lymphocytic Choriomeningitis Virus. In: Cantey J, (eds) Neonatal Infections. Springer, Cham. 2018. doi: 10.1007/978-3-319-90038-4_15.
Ramírez-Olivencia G, Estébanez M, Membrillo FJ, del Carmen Ybarra M. Use of ribavirin in viruses other than hepatitis C. A review of the evidence. Enfermedades infecciosas y microbiologia clinica (English ed). 2019; 37(9): 602-8.
Tian D, Liu Y, Liang C, Xin L, Xie X, Zhang D et al. An update review of emerging small-molecule therapeutic options for COVID-19. Biomed Pharmacother. 2021; 137: 111313.
Hickerson BT, Westover JB, Jung KH, Komeno T, Furuta Y, Gowen BB. Effective Treatment of Experimental Lymphocytic Choriomeningitis Virus Infection: Consideration of Favipiravir for Use With Infected Organ Transplant Recipients. J Infect Dis. 2018; 218(4): 522-7.
Herring S, Oda JM, Wagoner J, Kirchmeier D, O'Connor A, Nelson EA et al. Inhibition of Arenaviruses by Combinations of Orally Available Approved Drugs. Antimicrob Agents Chemother. 2021; 65(4): e01146-20. doi: 10.1128/AAC.01146-20.
Indari O, Jakhmola S, Manivannan E, Jha HC. An Update on Antiviral Therapy Against SARS-CoV-2: How Far Have We Come? Front Pharmacol. 2021; 12: 632677.
Mire CE, Cross RW, Geisbert JB, Borisevich V, Agans KN, Deer DJ et al. Human-monoclonal-antibody therapy protects nonhuman primates against advanced Lassa fever. Nat Med. 2017; 23(10): 1146-9.
Kumari V, Vishwas S, Kumar R, Kakoty V, Khursheed R, Babu MR et al. An overview of biomedical applications for gold nanoparticles against lung cancer. J Drug Delivery Sci Technol. 2023; 86: 104729. doi: 10.1016/j.jddst.2023.104729.
Kaur A, Singh N, Kaur H, Kakoty V, Sharma DS, Khursheed R et al. Neurodegenerative disease and brain delivery of therapeutics: Bridging the gap using dendrimers. J Drug Delivery Sci Technol. 2023; 87: 104868. doi: 10.1016/j.jddst.2023.104868.
Dangi T, Chung YR, Palacio N, Penaloza-MacMaster P. Interrogating Adaptive Immunity Using LCMV. Curr Protoc Immunol. 2020; 130(1): e99.
Dangi T, Chung YR, Palacio N, Penaloza?MacMaster P. Interrogating adaptive immunity using LCMV. Current protocols in immunology. 2020; 130(1): e99.
Wilson MR, Peters CJ. Diseases of the central nervous system caused by lymphocytic choriomeningitis virus and other arenaviruses. Handbook Clin Neurol. 2014; 123: 671-81.
Cordey S, Sahli R, Moraz ML, Estrade C, Morandi L, Cherpillod P et al. Analytical validation of a lymphocytic choriomeningitis virus real-time RT-PCR assay. J Virol Methods. 2011; 177(1): 118-22.
Caddy SL, Vaysburd M, Papa G, Wing M, O'Connell K, Stoycheva D et al. Viral nucleoprotein antibodies activate TRIM21 and induce T-cell immunity. Embo J. 2021; 40(5): e106228.
Caddy SL, Vaysburd M, Papa G, Wing M, O'Connell K, Stoycheva D et al. Viral nucleoprotein antibodies activate TRIM21 and induce T-cell immunity. EMBOJ. 2021; 40(5): e106228.
Matz HC, McIntire KM, Ellebedy AH. Persistent germinal center responses: slow-growing trees bear the best fruits. Curr Opin Immunol. 2023; 83: 102332.
Fallet B, Hao Y, Florova M, Cornille K, de Los Aires AV, Girelli Zubani G et al. Chronic Viral Infection Promotes Efficient Germinal Center B Cell Responses. Cell Rep. 2020; 30(4): 1013-26.e7.
Takimoto K, Taharaguchi M, Morikawa S, Ike F, Yamada YK. Detection of the antibody to lymphocytic choriomeningitis virus in sera of laboratory rodents infected with viruses of laboratory and newly isolated strains by ELISA using purified recombinant nucleoprotein. Exp Anim. 2008; 57(4): 357-65.
He X, Yang F, Wu Y, Lu J, Gao X, Zhu X et al. Identification of tanshinone I as cap-dependent endonuclease inhibitor with broad-spectrum antiviral effect. J Virol. 2023; 97(10): e0079623. doi: 10.1128/jvi.00796-23. Epub 2023 Sep 21.
Ryu WS. Diagnosis and Methods. Mol Virol Human Pathogen Virus. 2017; 47-62.
Elschner MC, Laroucau K, Singha H, Tripathi BN, Saqib M, Gardner I et al. Evaluation of the comparative accuracy of the complement fixation test, Western blot and five enzyme-linked immunosorbent assays for serodiagnosis of glanders. PLoS One. 2019; 14(4): e0214963.
Dimech W. The standardization and control of serology and nucleic acid testing for infectious diseases. Clin Microbiol Rev. 2021; 34(4): e0003521.
Premraj A, Aleyas AG, Nautiyal B, Rasool TJ. Nucleic acid and immunological diagnostics for SARS-CoV-2: Processes, platforms and pitfalls. Diagnostics. 2020; 10(11): 866.
Makvandi M, Teimoori A, Nahad MP, Khodadadi A, Zandi M. Expression of Salmonella typhimurium and Escherichia coli flagellin protein and its functional characterization as an adjuvant. Microb Pathogen. 2018; 118: 87-90.
Artika IM, Dewi YP, Nainggolan IM, Siregar JE, Antonjaya U. Real-time polymerase chain reaction: current techniques, applications, and role in COVID-19 diagnosis. Genes. 2022; 13(12): 2387.
Satterfield BC, Kulesh DA, Norwood DA, Wasieloski LP Jr, Caplan MR, West JA. Tentacle Probes: differentiation of difficult single-nucleotide polymorphisms and deletions by presence or absence of a signal in real-time PCR. Clin Chem. 2007; 53(12): 2042-50.
Melnik LI. Lassa virus countermeasures. Curr Top Microbiol Immunol. 2023; 440: 111-145. doi: 10.1007/82_2022_261.
Pankovics P, Nagy A, Nyul Z, Juhász A, Takáts K, Boros Á et al. Human cases of lymphocytic choriomeningitis virus (LCMV) infections in Hungary. Arch Virol. 2023; 168(11): 275.
de Vries M, Deijs M, Canuti M, van Schaik BD, Faria NR, van de Garde MD et al. A sensitive assay for virus discovery in respiratory clinical samples. PLoS One. 2011; 6(1): e16118.
Ferdinand AS, Kelaher M, Lane CR, da Silva AG, Sherry NL, Ballard SA, Andersson P, Hoang T, Denholm JT, Easton M, Howden BP. An implementation science approach to evaluating pathogen whole genome sequencing in public health. Genome Med. 2021; 13: 1-1.
Didelot X, Bowden R, Wilson DJ, Peto TEA, Crook DW. Transforming clinical microbiology with bacterial genome sequencing. Nat Rev Genet. 2012; 13(9): 601-12.
Palacios G, Druce J, Du L, Tran T, Birch C, Briese T et al. A new arenavirus in a cluster of fatal transplant-associated diseases. N Engl J Med. 2008; 358(10): 991-8.
Zhong Y, Xu F, Wu J, Schubert J, Li MM. Application of next generation sequencing in laboratory medicine. Ann Lab Med. 2021; 41(1): 25-43.
Miller JR, Koren S, Sutton G. Assembly algorithms for next-generation sequencing data. Genomics. 2010; 95(6): 315-27.
Naccache SN, Federman S, Veeraraghavan N, Zaharia M, Lee D, Samayoa E et al. A cloud-compatible bioinformatics pipeline for ultrarapid pathogen identification from next-generation sequencing of clinical samples. Genome Res. 2014; 24(7): 1180-92.
Choudhary S, Satija R. Comparison and evaluation of statistical error models for scRNA-seq. Genome Biology. 2022; 23(1): 27.
Taylor DL, Jackson AU, Narisu N, Hemani G, Erdos MR, Chines PS et al. Integrative analysis of gene expression, DNA methylation, physiological traits, and genetic variation in human skeletal muscle. Proc Nat Acad Sci. 2019; 116(22): 10883-8.
Chhabra P, Browne H, Huynh T, Diez-Valcarce M, Barclay L, Kosek MN et al. Single-step RT-PCR assay for dual genotyping of GI and GII norovirus strains. J Clin Virol. 2021; 134: 104689.
Xiang H, Wen X, Wen Y, Zhang H, Cao S, Huang X et al. Development and application of a visual microarray for synchronously detecting H5N1, H7N9 and H9N2 avian influenza virus RNA. J Virol Methods. 2022; 301: 114371.
Klaassen CH, Prinsen CF, de Valk HA, Horrevorts AM, Jeunink MA, Thunnissen FB. DNA microarray format for detection and subtyping of human papillomavirus. J Clin Microbiol. 2004; 42(5): 2152-60.
Vink JN, Hayhurst M, Gerth ML. Harnessing CRISPR-Cas for oomycete genome editing. Trends in Microbiology. 2023 Apr 30.
Ophinni Y, Inoue M, Kotaki T, Kameoka M. CRISPR/Cas9 system targeting regulatory genes of HIV-1 inhibits viral replication in infected T-cell cultures. Scientif Rep. 2018; 8(1): 7784.
Price AA, Sampson TR, Ratner HK, Grakoui A, Weiss DS. Cas9-mediated targeting of viral RNA in eukaryotic cells. Proc Nat Acad Sci. 2015; 112(19): 6164-9.
Martinez MG, Combe E, Inchauspe A, Mangeot PE, Delberghe E, Chapus F et al. CRISPR-Cas9 targeting of hepatitis B virus covalently closed circular DNA generates transcriptionally active episomal variants. Mbio. 2022; 13(2): e0288821.
Shmakov S, Abudayyeh OO, Makarova KS, Wolf YI, Gootenberg JS, Semenova E et al. Discovery and functional characterization of diverse class 2 CRISPR-Cas systems. Mol Cell. 2015; 60(3): 385-97.
Gootenberg JS, Abudayyeh OO, Kellner MJ, Joung J, Collins JJ, Zhang F. Multiplexed and portable nucleic acid detection platform with Cas13, Cas12a, and Csm6. Science. 2018; 360(6387): 439-44.
Myhrvold C, Freije CA, Gootenberg JS, Abudayyeh OO, Metsky HC, Durbin AF et al. Field-deployable viral diagnostics using CRISPR-Cas13. Science. 2018; 360(6387): 444-8.
Gootenberg JS, Abudayyeh OO, Lee JW, Essletzbichler P, Dy AJ, Joung J et al. Nucleic acid detection with CRISPR-Cas13a/C2c2. Science. 2017; 356(6336): 438-42.
Zandi M, Hosseini F, Adli AH, Salmanzadeh S, Behboudi E, Halvaei P et al. State-of-the-art cerium nanoparticles as promising agents against human viral infections. Biomed Pharmacother. 2022; 156: 113868.
Halvaei P, Zandi S, Zandi M. Biosensor as a novel alternative approach for early diagnosis of monkeypox virus. Int J Surg. 2023; 109(1): 50-2.
Zhou LY, Qin Z, Zhu YH, He ZY, Xu T. Current RNA-based therapeutics in clinical trials. Curr Gene Ther. 2019; 19(3): 172-96.
Berber B, Aydin C, Kocabas F, Guney-Esken G, Yilancioglu K, Karadag-Alpaslan M et al. Gene editing and RNAi approaches for COVID-19 diagnostics and therapeutics. Gene Ther. 2021; 28(6): 290-305.
Tevaearai F, Moser L, Pomar L. Prenatal Diagnosis of Congenital Lymphocytic Choriomeningitis Virus Infection: A Case Report. Viruses. 2022; 14(11): 2586.
Pencole L, Sibiude J, Weingertner AS, Mandelbrot L, Vauloup-Fellous C, Picone O. Congenital lymphocytic choriomeningitis virus: A review. Prenat Diagn. 2022; 42(8): 1059-69.
Schwendinger M, Thiry G, De Vos B, Leroux-Roels G, Bruhwyler J, Huygens A et al. A randomized dose-escalating phase I trial of a replication-deficient lymphocytic choriomeningitis virus vector-based vaccine against human cytomegalovirus. J Infect Dis. 2022; 225(8): 1399-410.
Anesi JA, Silveira FP, AST Infectious Diseases Community of Practice. Arenaviruses and West Nile virus in solid organ transplant recipients: guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019; 33(9): e13576.
Vilibic-Cavlek T, Oreski T, Korva M, Kolaric B, Stevanovic V, Zidovec-Lepej S et al. Prevalence and risk factors for lymphocytic choriomeningitis virus infection in continental Croatian regions. Trop Med Infect Dis. 2021; 6(2): 67.
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