Arenaviruses

Lassa fever, a viral hemorrhagic fever endemic in parts of West Africa, is a severe febrile illness transmitted to humans by the rodent Mastomys natalensis. To determine risk of Lassa fever in households in Sierra Leonean refugee camps, we analyzed the spatial relationships between households with a Lassa case and focal locations of potential rodent habitats. Quality and hygiene factors of households were assessed to determine possible risk factors for household rodent infestation and occurrence of Lassa fever. The odds to have a rat burrow were higher in case houses than in control houses (OR 24, 95% CI 6.0–93). Case houses scored significantly worse in the quality of housing and external hygiene. These findings suggest that risk of Lassa fever in refugee camps depends on individual housing quality and the hygiene of the immediate surrounding environment.

Forty-eight Sigmodon alstoni (Alston's cotton rat) were inoculated with Caño Delgadito (CDG) virus to extend our knowledge and understanding of the natural host relationships of the hantaviruses indigenous to the Americas. Infectious CDG virus was recovered from oropharyngeal secretions, urine, or solid tissues of nine of 12 animals killed on day 9 post-inoculation (PI), 14 of 24 animals killed on day 18 or 27 PI, and none of 12 animals killed on day 54 PI. In addition, virus-specific RNA was detected in the kidneys of six of the 12 animals killed on day 54 PI, and adult cotton rats inoculated with the kidneys of four animals killed on day 54 PI developed antibody to CDG virus. Collectively, the results indicate that CDG virus can establish lengthy (perhaps lifelong) infections in Alston's cotton rat and thus support the concept that S. alstoni is the principal host of CDG virus.

The Whitewater Arroyo virus (WWA) is a newly described North American arenavirus. The purpose of this study was to elucidate the biology of this virus in its natural rodent host, Neotoma albigula (white-throated woodrat). Thirteen adult, 7 juvenile, and 8 newborn woodrats each were inoculated subcutaneously with 1,000 cell culture infectious dose50 of the WWA virus prototype strain AV 9310135. All 28 animals became infected (as measured by the recovery of infectious virus and/or seroconversion) and no overt illness was associated with infection. Infection and virus shedding in the adult animals were transient (less than 59 days) whereas virus shedding in animals inoculated at birth persisted through 164 days of age. These results indicate that the duration of WWA virus infection in N. albigula is dependent upon the animal's age at the onset of infection and that neonatal infection can result in chronic (perhaps lifelong) virus shedding.

The purpose of this study was to extend our knowledge on the geographic and natural rodent host ranges of New World arenaviruses in California. Sera from 1,094 sigmodontine and 112 murine rodents were tested for antibody against Whitewater Arroyo and Amapari viruses. Antibody was found in 55 (4.6%) of the 1,206 rodents: 4 from northwestern San Diego County, 3 from Los Angeles County, and 48 from Orange County. The antibody-positive rodents included 8 (7.8%) of 103 Neotoma fuscipes, 1 (0.6%) of 180 Neotoma lepida, 1 (3.1%) of 32 Peromyscus boylii, 8 (11.0%) of 73 Peromyscus californicus, 1 (1.2%) of 85 Peromyscus eremicus, 30 (8.5%) of 353 Peromyscus maniculatus, and 6 (2.2%) of 268 Reithrodontomys megalotis. This study provides the first evidence that New World arenaviruses occur in Los Angeles and Orange counties and northwestern San Diego County, and the first evidence that Peromyscus and Reithrodontomys species are naturally infected with New World arenaviruses.

The established animal model for Lassa fever is based on the new world arenavirus Pichinde (PIC). Natural isolates of PIC virus are attenuated in guinea pigs, but serial guinea pig passage renders them extremely virulent in that host. We have compared the nucleotide sequences of the small RNA segments of two attenuated, low-passage variants of the PIC virus Munchique strain (CoAn 4763) and two virulent, high-passage derivatives. Missense mutations in the glycoprotein precursor (GPC) gene at codons GPC-119, GPC-140, and GPC-164 and the nucleoprotein gene (NP) codons NP-35 and NP-374 were most closely associated with virulence. Codon GPC-140 is predicted to represent a region of peak hydrophilicity of the glycoprotein 1 (GP1); it is conceivable that mutations at this site could influence virulence by altering B cell epitopes or virus attachment protein conformation.