Arenaviruses: New World and Old World — Questions

The pathogenic New World (clade B) arenaviruses enter cells through transferrin receptor 1, whereas the Old World viruses and clade C use alpha-dystroglycan.

Sialic acid, CD4 and angiotensin-converting enzyme 2 are receptors for other viruses, not the arenaviruses.

About a quarter to a third of survivors of clinical Lassa fever develop sensorineural hearing loss, often permanent, making Lassa a leading cause of acquired deafness in its endemic region.

The other complications listed are not characteristic sequelae of Lassa fever.

The live-attenuated Junin vaccine Candid #1, in use since the late 1980s, has sharply reduced Argentine haemorrhagic fever.

Ribavirin and immune plasma are treatments rather than population-level control, the rodent reservoir has not been eliminated, and there is no inactivated Lassa vaccine nor a mosquito vector to target.

The South American arenaviral haemorrhagic fevers feature prominent neurological signs, such as tremor and ataxia, more than Lassa fever does.

Deafness is the Lassa sequela, chronic human carriage does not occur, a rash is common, and arenaviruses are not mosquito-transmitted.

In the adult mouse the fatal disease is caused by the cytotoxic T-lymphocyte response, the classic demonstration that a virus-specific T-cell response can mediate immunopathology as well as viral clearance.

It is not due to direct neuronal lysis, antibody or complement, bacterial superinfection or immune-complex vasculitis.

Congenital lymphocytic choriomeningitis virus infection causes fetal death, hydrocephalus and chorioretinitis, so it belongs in the differential of congenital infection.

The virus does not typically cause adult haemorrhagic fever, tick-borne encephalitis, post-transfusion hepatitis or chronic renal failure.

The hepatic injury of Lassa fever is a direct viral cytopathic effect, with multifocal hepatocellular necrosis and little inflammation, unlike the immunopathology of lymphocytic choriomeningitis.

It is not immune-complex, coagulation-driven, autoimmune or purely ischaemic in origin.

All the pathogenic New World arenaviruses, Junin, Machupo, Guanarito, Sabia and Chapare, fall in clade B.

Clades A and C contain no confirmed human pathogens, and the Old World complex and the reptile-associated genus are separate groups.

The ambisense arrangement lets the virus express its genes in a set temporal order, making the nucleoprotein and polymerase first and the glycoprotein and matrix protein later.

Arenaviruses do not integrate, reverse transcribe or reassort with influenza, and the genome cannot be translated directly.

The virions take up host ribosomes during assembly, giving the grainy, sand-like appearance that names the family.

The grains are not glycoprotein crystals, calcified bodies or lipid droplets, and the appearance is unrelated to nucleocapsid symmetry.

Lassa virus is maintained by the multimammate rat Mastomys natalensis, a peridomestic rodent that sheds virus in urine in and around houses.

The house mouse is the lymphocytic choriomeningitis reservoir, Calomys rodents carry the New World agents, and ticks and bats are not arenavirus reservoirs.

Lujo virus is the arenavirus that emerged within southern Africa, in the 2008 Johannesburg nosocomial cluster, and like the other haemorrhagic arenaviruses it is handled at biosafety level 4.

Junin, Guanarito and Machupo are New World agents of the Americas, and Tacaribe is a non-pathogenic bat-associated virus.

Lassa virus is the arenavirus most noted for person-to-person and nosocomial transmission, through contact with infected blood and body fluids.

Lymphocytic choriomeningitis, Tacaribe, Latino and Mopeia viruses are not significant causes of human-to-human spread.

Unlike the Old World arenaviruses, Junin and Machupo cause disease in their Calomys rodent hosts, including haemolytic anaemia and reduced fertility, which helps regulate the shedding population.

Arenaviruses are rodent-borne rather than tick-borne, are shed in urine, establish persistent infection, and use rodents rather than bats as reservoirs.

Immunoglobulin M can persist for months after Lassa fever, so its presence does not confirm acute infection, which is better shown by antigen detection or reverse transcription polymerase chain reaction.

IgM does develop, the virus is immunogenic, molecular testing does not require maximum containment, and malaria cross-reaction is not the issue.