Junín virus and Argentine haemorrhagic fever: Virology, pathogenesis, diagnosis, and prevention strategies

Table 1 Timeline of Junín virus discovery and major outbreaks

Year	Event
1953	First recognized cases of a hemorrhagic illness among agricultural workers in the Pampas region of Argentina
1958	Isolation and identification of the causative agent, later named Junín virus, in Junín province, Argentina
1960s	Epidemiological studies confirmed rodent reservoirs, particularly Calomys musculinus, as the natural host of the virus
1970s	Development of early diagnostic techniques and experimental treatments, including immune plasma therapy
1980s	Research programs intensified to develop a vaccine for Argentine hemorrhagic fever
1990	Development of the Candid #1 live attenuated vaccine through collaboration between Argentina and international research institutions
1991	Large-scale vaccination campaigns initiated in endemic regions of Argentina
2000s	Improvements in molecular diagnostic methods such as RT-PCR for rapid detection of Junín virus infection
2010s	Advances in molecular virology and reverse genetics improved understanding of viral replication and pathogenesis
2020s	Continued surveillance and research on arenaviruses, including genomic studies and development of new antiviral strategies

Table 2 Laboratory diagnostic methods for Junín virus infection

Diagnostic method	Principle	Specimen	Optimal timing	Advantages	Limitations	Ref.
RT-PCR	Detection and amplification of Junín viral RNA after reverse transcription	Whole blood, serum, plasma, occasionally tissue samples	Early acute phase (first 7-10 days during viremia)	Highly sensitive and specific; rapid confirmation of active infection; widely used in reference laboratories	Requires specialized molecular equipment and trained personnel; contamination risk; limited availability in rural endemic settings	[2,4]
Real-time RT-PCR (qRT-PCR)	Quantitative detection of viral RNA using fluorescent probes during amplification	Whole blood, serum, plasma	Early acute phase	Rapid and highly sensitive; allows quantification of viral load and monitoring of disease progression	Expensive instrumentation; requires advanced molecular laboratory infrastructure	[2,4]
Virus isolation	Cultivation of infectious virus in susceptible cell cultures (e.g., Vero cells)	Blood, serum, tissue samples	Early stage of infection when viremia is present	Gold standard for confirmation; enables viral characterization, sequencing, and research studies	Requires biosafety level-4 containment; slow and labor-intensive; high biohazard risk; rarely used for routine diagnosis	[2,3,13]
IgM ELISA	Detection of virus-specific IgM antibodies generated during the early immune response	Serum or plasma	From end of first week of illness onward	Indicates recent infection; relatively simple, cost-effective, and widely used for screening	Not suitable for very early infection; possible cross-reactivity with other arenaviruses	[2,4,8,9]
IgG ELISA	Detection of virus-specific IgG antibodies indicating immune response or past exposure	Serum or plasma	Late acute phase or convalescent stage	Useful for seroepidemiological studies, vaccine evaluation, and confirmation of seroconversion	Cannot diagnose early infection; often requires paired sera samples	[1,2,4,10]
Antigen detection assays	Detection of viral proteins using specific monoclonal or polyclonal antibodies	Blood, serum, plasma	Early phase of infection	Faster than serological tests; useful when molecular testing is unavailable	Lower sensitivity compared with PCR; limited commercial availability	[2,4,9]
Neutralization test (PRNT)	Measurement of virus-neutralizing antibodies capable of inhibiting viral infectivity	Serum	Convalescent phase	Highly specific; considered reference method for assessing protective immunity and vaccine response	Requires live virus and high-containment laboratory; technically demanding and time-consuming	[1,10,18,22,23]
Routine laboratory tests (supportive)	Detection of hematological and biochemical abnormalities associated with infection	Whole blood, urine	Any stage of illness	Supports clinical suspicion (e.g., thrombocytopenia, leukopenia, elevated liver enzymes, proteinuria)	Nonspecific; cannot confirm Junín virus infection	[4,8,9]

RT-PCR: Reverse transcription polymerase chain reaction; qRT-PCR: Quantitative reverse transcription polymerase chain reaction; RNA: Ribonucleic acid; IgM ELISA: Immunoglobulin M enzyme-linked immunosorbent assay; IgG ELISA: Immunoglobulin G enzyme-linked immunosorbent assay; PRNT: Plaque reduction neutralization test.

Table 3 Comparative virological, epidemiological, and clinical characteristics of major arenaviruses associated with human disease

Feature	Genus group	Geographic region	Associated disease	Genome type	Genome segments	Reservoir host	Primary transmission	Cell receptor used	Pathogenesis pattern	Case fatality rate (untreated)	Human-to-human transmission	Typical outbreak pattern	Vaccine availability	Biosafety level	Ref.
Machupo virus	New world	Bolivia	Bolivian Hemorrhagic Fever	Bi-segmented ambisense ssRNA	L (polymerase, Z) and S (NP, GP)	Calomys callosus	Rodent excreta	Transferrin receptor-1	Immune suppression; vascular leakage	20%-30%	Rare	Rural agricultural areas	None	BSL-4	[3,6,7,27,29]
Junín virus	New world	Argentina	Argentine Hemorrhagic Fever	Same	Same	Calomys musculinus	Rodent exposure	Transferrin receptor-1	Similar to Machupo	15%-30%	Limited	Rural Argentina	Candid #1 vaccine	BSL-4	[1-4,8,12,13]
Lassa virus	Old world	West Africa	Lassa Fever	Same	Same	Mastomys natalensis	Rodent contact + human-to-human	α-Dystroglycan	High viremia; immune suppression	1%-20%	Common	Endemic seasonal outbreaks	None widely licensed	BSL-4	[31]
Guanarito virus	New world	Venezuela	Venezuelan hemorrhagic fever	Same	Same	Zygodontomys brevicauda	Rodent exposure	Transferrin receptor-1	Similar to Machupo	20%-30%	Rare	Rural Venezuela	None	BSL-4	[6,23,28,32]
Sabiá virus	New world	Brazil	Brazilian hemorrhagic fever	Same	Same	Suspected rodent	Rodent exposure	Transferrin receptor-1	Limited data; similar NW pattern	High (limited data)	Rare	Sporadic cases	None	BSL-4	[6,23,26,34]
Chapare virus	New world	Bolivia	Chapare hemorrhagic fever	Same	Same	Suspected rodent	Rodent + healthcare transmission	Likely transferrin receptor-1	Hemorrhagic disease; immune dysregulation	High in outbreaks	Confirmed	Small outbreaks (2004, 2019)	None	BSL-4	[6,23,27,34]
Lujo virus	Old world lineage	Zambia/Southern Africa	Lujo Hemorrhagic Fever	Same	Same	Suspected rodent	Rodent + nosocomial spread	Unclear/distinct receptor	Severe systemic inflammation	About 80% (2008 outbreak)	Confirmed	Single major outbreak (2008)	None	BSL-4	[33]
LCMV	Old world	Worldwide	Aseptic meningitis/encephalitis	Same	Same	Mus musculus	Rodent exposure; vertical; transplant	α-Dystroglycan	Immune-mediated CNS inflammation	< 1% in healthy adults	Rare	Sporadic global cases	None	BSL-3 (BSL-4 recommended for high-risk work)	[8]

BSL: Biosafety level; CNS: Central nervous system; LCMV: Lymphocytic choriomeningitis virus.