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Emerging Infectious Diseases May 2024We detected Mayaro virus (MAYV) in 3.4% (28/822) of febrile patients tested during 2018-2021 from Roraima State, Brazil. We also isolated MAYV strains and confirmed that...
We detected Mayaro virus (MAYV) in 3.4% (28/822) of febrile patients tested during 2018-2021 from Roraima State, Brazil. We also isolated MAYV strains and confirmed that these cases were caused by genotype D. Improved surveillance is needed to better determine the burden of MAYV in the Amazon Region.
Topics: Humans; Brazil; Molecular Epidemiology; Fever; Male; Phylogeny; Adult; Alphavirus; Female; Genotype; Child; Middle Aged; Adolescent; Child, Preschool; History, 21st Century; Young Adult; Aged; Arenaviridae Infections; Alphavirus Infections; Infant
PubMed: 38666638
DOI: 10.3201/eid3005.231406 -
Emerging Microbes & Infections Dec 2024The Natal multimammate mouse () is the host of Lassa mammarenavirus, causing Lassa haemorrhagic fever in West Africa. As there is currently no operational vaccine and...
The Natal multimammate mouse () is the host of Lassa mammarenavirus, causing Lassa haemorrhagic fever in West Africa. As there is currently no operational vaccine and therapeutic drugs are limited, we explored rodent control as an alternative to prevent Lassa virus spillover in Upper Guinea, where the disease is highly endemic in rural areas. In a seven-year experiment, we distributed rodenticides for 10-30 days once a year and, in the last year, added intensive snap trapping for three months in all the houses of one village. We also captured rodents both before and after the intervention period to assess their effectiveness by examining alterations in trapping success and infection rates (Lassa virus RNA and IgG antibodies). We found that both interventions reduced the rodent population by 74-92% but swiftly rebounded to pre-treatment levels, even already six months after the last snap-trapping control. Furthermore, while we observed that chemical control modestly decreased Lassa virus infection rates annually (a reduction of 5% in seroprevalence per year), the intensive trapping unexpectedly led to a significantly higher infection rate (from a seroprevalence of 28% before to 67% after snap trapping control). After seven years, we conclude that annual chemical control, alone or with intensive trapping, is ineffective and sometimes counterproductive in preventing Lassa virus spillover in rural villages. These unexpected findings may result from density-dependent breeding compensation following culling and the survival of a small percentage of chronically infected rodents that may spread the virus to a new susceptible generation of mice.
Topics: Mice; Animals; Lassa virus; Guinea; Rodent Control; Seroepidemiologic Studies; Disease Reservoirs; Lassa Fever; Murinae; Africa, Western
PubMed: 38597241
DOI: 10.1080/22221751.2024.2341141 -
Emerging Infectious Diseases Sep 2023Lymphocytic choriomeningitis virus is an underreported cause of miscarriage and neurologic disease. Surveillance remains challenging because of nonspecific...
Lymphocytic choriomeningitis virus is an underreported cause of miscarriage and neurologic disease. Surveillance remains challenging because of nonspecific symptomatology, inconsistent case reporting, and difficulties with diagnostic testing. We describe a case of acute lymphocytic choriomeningitis virus disease in a person living with HIV in Connecticut, USA, identified by using quantitative reverse transcription PCR.
Topics: Humans; Female; Pregnancy; Lymphocytic choriomeningitis virus; Connecticut; Lymphocytic Choriomeningitis; Abortion, Spontaneous; HIV Infections
PubMed: 37610188
DOI: 10.3201/eid2909.230087 -
Vaccine Mar 2024Lassa fever (LF) is a zoonotic viral hemorrhagic disease endemic to several West African countries. Approximately 300-500,000 cases occur annually across all ages with...
Lassa fever (LF) is a zoonotic viral hemorrhagic disease endemic to several West African countries. Approximately 300-500,000 cases occur annually across all ages with 10-20% case fatality rates. A LF vaccine is a recognized public health priority, with several candidates entering clinical trials. However, the perspectives of regional experts regarding critical vaccine properties, ideal delivery methods, and priority target populations remain unclear. Using a mixed methods approach with a standardized questionnaire, we individually interviewed 8 West African stakeholders, each with extensive knowledge and experience of LF. They strongly favored the use of a mass, proactive campaign strategy to immunize a wide age range of people in high-risk areas, including pregnant women and health care workers. We estimated that these and other plausible delivery scenarios could result in an initial demand of anywhere from 1 to 100 million doses, with most demand coming from Nigeria. These findings may help inform LF vaccine development and deployment efforts.
Topics: Humans; Female; Pregnancy; Lassa Fever; Lassa virus; Africa, Western; Nigeria; Viral Vaccines
PubMed: 38369392
DOI: 10.1016/j.vaccine.2024.02.044 -
BioRxiv : the Preprint Server For... Dec 2023Lassa virus (LASV), a mammarenavirus from , is the causative agent of Lassa fever (LF) endemic in West Africa. Currently, there are no vaccines or antivirals approved...
Lassa virus (LASV), a mammarenavirus from , is the causative agent of Lassa fever (LF) endemic in West Africa. Currently, there are no vaccines or antivirals approved for LF. The RNA-dependent RNA polymerases (RdRp) of RNA viruses are error-prone. As a negative-sense RNA virus, how LASV copes with errors in RNA synthesis and ensures optimal RNA replication are not well elucidated. LASV nucleoprotein (NP) contains a DEDDH 3'-to-5' exoribonuclease motif (ExoN), which is known to be essential for LASV evasion of the interferon response via its ability to degrade virus-derived double-stranded RNA. Herein, we present evidence that LASV NP ExoN has an additional function important for viral RNA replication. We rescued an ExoN-deficient LASV mutant (ExoN- rLASV) by using a reverse genetics system. Our data indicated that abrogation of NP ExoN led to impaired LASV growth and RNA replication in interferon-deficient cells as compared with wild-type rLASV. By utilizing PacBio Single Molecule, Real-Time (SMRT) long-read sequencing technology, we found that rLASV lacking ExoN activity was prone to producing aberrant viral genomic RNA with structural variations. In addition, NP ExoN deficiency enhanced LASV sensitivity to mutagenic nucleoside analogues in virus titration assay. Next-generation deep sequencing analysis showed increased single nucleotide substitution in ExoN- LASV RNA following mutagenic 5-flurouracil treatment. In conclusion, our study revealed that LASV NP ExoN is required for efficient viral RNA replication and mutation control. Among negative-sense RNA viruses, LASV NP is the first example that a viral protein, other than the RdRp, contributes to reduce errors in RNA replication and maintain genomic RNA integrity. These new findings promote our understanding of the basics of LASV infection and inform antiviral and vaccine development.
PubMed: 37090668
DOI: 10.1101/2023.04.12.536665 -
Emerging Microbes & Infections Dec 2024The spread of Lassa virus (LASV) in Guinea, Liberia and Sierra Leone, which together are named the Mano River Union (MRU) area, was examined phylogeographically. To...
The spread of Lassa virus (LASV) in Guinea, Liberia and Sierra Leone, which together are named the Mano River Union (MRU) area, was examined phylogeographically. To provide a reliable evolutionary scenario, new rodent-derived, whole LASV sequences were included. These were generated by metatranscriptomic next-generation sequencing from rodents sampled between 2003 and 2020 in 21 localities of Guinea and Sierra Leone. An analysis was performed using BEAST to perform continuous phylogeographic inference and EvoLaps v36 to visualize spatio-temporal spread. LASV was identified as expected in its primary host reservoir, the Natal multimammate mouse (), and also in two Guinean multimammate mice () in northern Sierra Leone and two rusty-bellied brush-furred mice () in southern Sierra Leone. This finding is consistent with the latter two species being secondary host reservoirs. The strains in these three species were very closely related in LASV lineage IV. Phylogenetic analysis indicated that the most recent common ancestor of lineage IV existed 316-374 years ago and revealed distinct, well-supported clades from Sierra Leone (Bo, Kabala and Kenema), Guinea (Faranah, Kissidougou-Guekedou and Macenta) and Liberia (Phebe-Ganta). The phylogeographic scenario suggests southern Guinea as the point of origin of LASV in the MRU area, with subsequent spread to towards Mali, Liberia and Sierra Leone at a mean speed of 1.6 to 1.1 km/year.
Topics: Mice; Animals; Lassa virus; Lassa Fever; Phylogeny; Africa, Western; Murinae
PubMed: 38047354
DOI: 10.1080/22221751.2023.2290834 -
Emerging Microbes & Infections Dec 2024Lassa virus (LASV), a risk-group 4 pathogen, must be handled in biosafety level-4 (BSL-4) conditions, thereby limiting its research and antiviral development. Here, we...
Lassa virus (LASV), a risk-group 4 pathogen, must be handled in biosafety level-4 (BSL-4) conditions, thereby limiting its research and antiviral development. Here, we developed a novel LASV reverse genetics system which, to our knowledge, is the first to study the complete LASV life cycle under BSL-2 conditions. Viral particles can be produced efficiently when LASV minigenomic RNA harbouring minimal viral -elements and reporter genes is transfected into a helper cell line stably expressing viral NP, GP, Z and L proteins. The resulting defective virions, named LASVmg, can propagate only in the helper cell line, providing a BSL-2 model to study the complete LASV life cycle. Using this model, we found that a previously reported cellular receptor α-dystroglycan is dispensable for LASVmg infection. Furthermore, we showed that ribavirin can inhibit LASVmg infection by inducing viral mutations. This new BSL-2 system should facilitate studying the LASV life cycle and screening antivirals.
Topics: Lassa virus; Reverse Genetics; Humans; Animals; Antiviral Agents; Chlorocebus aethiops; Cell Line; Virus Replication; Lassa Fever; Ribavirin; Vero Cells; Containment of Biohazards; Genome, Viral; Virion
PubMed: 38747061
DOI: 10.1080/22221751.2024.2356149 -
Emerging Infectious Diseases Jan 2024
Topics: Animals; Mice; Lymphocytic Choriomeningitis; Germany; Lymphocytic choriomeningitis virus
PubMed: 38147305
DOI: 10.3201/eid3001.230334 -
Viruses May 2024Immunotherapy with checkpoint inhibitors, albeit commonly used against tumors, is still at its infancy against chronic virus infections. It relies on the reinvigoration...
Immunotherapy with checkpoint inhibitors, albeit commonly used against tumors, is still at its infancy against chronic virus infections. It relies on the reinvigoration of exhausted T lymphocytes to eliminate virus-infected cells. Since T cell exhaustion is a physiological process to reduce immunopathology, the reinvigoration of these cells might be associated with an augmentation of pathological changes. To test this possibility, we here analyzed in the model system of chronic lymphocytic choriomeningitis virus (LCMV)-infected mice whether treatment with the checkpoint inhibitor anti-PD-L1 antibody would increase CD8 T cell-dependent fibrosis. We show that pre-existing spleen fibrosis did not worsen under conditions that increase CD8 T cell functionality and reduce virus loads suggesting that the CD8 T cell functionality increase remained below its pathogenicity threshold. These promising findings should further encourage immunotherapeutic trials against chronic virus infections.
Topics: Animals; Mice; Lymphocytic choriomeningitis virus; Immunotherapy; Lymphocytic Choriomeningitis; B7-H1 Antigen; CD8-Positive T-Lymphocytes; Fibrosis; Mice, Inbred C57BL; Immune Checkpoint Inhibitors; Viral Load; Spleen; Disease Models, Animal; Chronic Disease; Female
PubMed: 38793680
DOI: 10.3390/v16050799 -
Viruses Mar 2024CD8 T cells are critical to the adaptive immune response against viral pathogens. However, overwhelming antigen exposure can result in their exhaustion, characterised by...
CD8 T cells are critical to the adaptive immune response against viral pathogens. However, overwhelming antigen exposure can result in their exhaustion, characterised by reduced effector function, failure to clear virus, and the upregulation of inhibitory receptors, including programmed cell death 1 (PD-1). However, exhausted T cell responses can be "re-invigorated" by inhibiting PD-1 or the primary ligand of PD-1: PD-L1. Further, the absence of the type I interferon receptor IFNAR1 also results in T cell exhaustion and virus persistence in lymphocytic choriomeningitis virus Armstrong (LCMV-Arm)-infected mice. In this study, utilizing single- and double-knockout mice, we aimed to determine whether ablation of PD-1 could restore T cell functionality in the absence of IFNAR1 signalling in LCMV-Arm-infected mice. Surprisingly, this did not re-invigorate the T cell response and instead, it converted chronic LCMV-Arm infection into a lethal disease characterized by severe lung inflammation with an infiltration of neutrophils and T cells. Depletion of CD8 T cells, but not neutrophils, rescued mice from lethal disease, demonstrating that IFNAR1 is required to prevent T cell exhaustion and virus persistence in LCMV-Arm infection, and in the absence of IFNAR1, PD-L1 is required for survival. This reveals an important interplay between IFNAR1 and PD-L1 with implications for therapeutics targeting these pathways.
Topics: Mice; Animals; Lymphocytic choriomeningitis virus; CD8-Positive T-Lymphocytes; Lymphocytic Choriomeningitis; B7-H1 Antigen; Programmed Cell Death 1 Receptor; Mice, Knockout; Interferon Type I; Mice, Inbred C57BL
PubMed: 38543756
DOI: 10.3390/v16030390