Lassa mammarenavirus

It is endemic in West African countries, especially Sierra Leone, the Republic of Guinea, Nigeria, and Liberia, where the annual incidence of infection is between 300,000 and 500,000 cases, resulting in 5,000 deaths per year.

[4] In 1969, missionary nurse Laura Wine fell ill with a mysterious disease she contracted from an obstetrical patient in Lassa, a village in Borno State, Nigeria.

[7] Samples from Pinneo were sent to Yale University in New Haven where a new virus, that would later be known as Lassa mammarenavirus, was isolated for the first time by Jordi Casals-Ariet, Sonja Buckley, and others.

[17] The large segment encodes a small zinc finger protein (Z) that regulates transcription and replication,[18][19] and the RNA polymerase (L).

This temporal control allows the spike proteins to be produced last, and therefore, delay recognition by the host immune system.

[citation needed] Nucleotide studies of the genome have shown that Lassa has four lineages: three found in Nigeria and the fourth in Guinea, Liberia, and Sierra Leone.

Specific variants of the genes encoding these proteins appear to be under positive selection in West Africa where Lassa is endemic.

Once within the cell the viruses are rapidly delivered to endosomes via vesicular trafficking albeit one that is largely independent of the small GTPases Rab5 and Rab7.

Dystroglycan, which is later cleaved into alpha-dystroglycan and beta-dystroglycan is originally expressed in most cells to mature tissues, and it provides molecular link between the ECM and the actin-based cytoskeleton.

[24] After the virus enters the cell by alpha-dystroglycan mediated endocytosis, the low-pH environment triggers pH-dependent membrane fusion and releases RNP (viral ribonucleoprotein) complex into the cytoplasm.

The symptoms include flu-like illness characterized by fever, general weakness, cough, sore throat, headache, and gastrointestinal manifestations.

[26][27][28] In 2012 it was reported how Lassa mammarenavirus nucleoprotein (NP) sabotages the host's innate immune system response.

Generally, when a pathogen enters into a host, innate defense system recognizes the pathogen-associated molecular patterns (PAMP) and activates an immune response.

NP encoded in Lassa mammarenavirus is essential in viral replication and transcription, but it also suppresses host innate IFN response by inhibiting translocation of IRF-3.

Lassa virus structure and genome.Figure by Fehling et al., 2012 [ 13 ]
Entry mechanisms of Old World and New World arenaviruses.
Lassa virus life cycle. Figure by Fehling et al., 2012 [ 13 ]
False color Scanning electron micrograph of Lassa virus (in orange) budding off an infected cell