Host-Species Transferrin Receptor 1 Orthologs Are Cellular Receptors for Nonpathogenic New World Clade B Arenaviruses

The ability of a New World (NW) clade B arenavirus to enter cells using human transferrin receptor 1 (TfR1) strictly correlates with its ability to cause hemorrhagic fever. Amapari (AMAV) and Tacaribe (TCRV), two nonpathogenic NW clade B arenaviruses that do not use human TfR1, are closely related to the NW arenaviruses that cause hemorrhagic fevers. Here we show that pseudotyped viruses bearing the surface glycoprotein (GP) of AMAV or TCRV can infect cells using the TfR1 orthologs of several mammalian species, including those of their respective natural hosts, the small rodent Neacomys spinosus and the fruit bat Artibeus jamaicensis. Mutation of one residue in human TfR1 makes it a functional receptor for TCRV, and mutation of four residues makes it a functional receptor for AMAV. Our data support an in vivo role for TfR1 in the replication of most, if not all, NW clade B arenaviruses, and suggest that with modest changes in their GPs the nonpathogenic arenaviruses could use human TfR1 and emerge as human pathogens

Diversity Among Tacaribe Serocomplex Viruses (Family Arenaviridae) Naturally Associated with the White-Throated Woodrat (Neotoma albigula) in the Southwestern United States

Bayesian analyses of glycoprotein precursor and nucleocapsid protein gene sequences indicated that arenaviruses naturally associated with white-throated woodrats in central Arizona are phylogenetically closely related to the Whitewater Arroyo virus prototype strain AV 9310135, which originally was isolated from a white-throated woodrat captured in northwestern New Mexico. Pairwise comparisons of glycoprotein precursor and nucleocapsid protein amino acid sequences revealed extensive diversity among arenaviruses isolated from white-throated woodrats captured in different counties in central Arizona and extensive diversity between these viruses and Whitewater Arroyo virus strain AV 9310135. It was concluded that the viruses isolated from the white-throated woodrats captured in Arizona represent 2 novel species (Big Brushy Tank virus and Tonto Creek virus) and that these species should be included with Whitewater Arroyo virus in a species complex within the Tacaribe serocomplex (family Arenaviridae, genus Arenavirus)

Antibodies to Tacaribe Serocomplex Viruses (Family Arenaviridae, Genus Arenavirus) in Cricetid Rodents from New Mexico, Texas, and Mexico

Blood samples from 4893 cricetid rodents were tested for antibody (immunoglobulin G) to Whitewater Arroyo virus and Amaparí virus to extend our knowledge of the natural host range and geographical distribution of Tacaribe serocomplex viruses in North America. Antibodies to arenaviruses were found in northern pygmy mice (Baiomys taylori), woodrats (Neotoma spp.), northern grasshopper mice (Onychomys leucogaster), oryzomys (Oryzomys spp.), deermice (Megadontomys nelsoni and Peromyscus spp.), harvest mice (Reithrodontomys spp.), and cotton rats (Sigmodon spp.) captured in New Mexico, Texas, or Mexico. Comparison of endpoint antibody titers to Whitewater Arroyo virus and Amaparí virus in individual blood samples indicated that the Tacaribe complex viruses enzootic in Texas and Mexico are antigenically diverse

Pathology of Black Creek Canal Virus Infection in Juvenile Hispid Cotton Rats (Sigmodon hispidus)

The purpose of this study was to assess the effect of inoculum dose on the pathogenesis of Black Creek Canal virus (BCCV) infection in the hispid cotton rat (Sigmodon hispidus), the principal host of BCCV. No sign of illness was observed in any of the 52 juvenile hispid cotton rats inoculated with 3.1, 1.1, −0.9, or −2.9 log10 median infectious dosesVeroE6 (ID50-VeroE6) of BCCV and euthanized on day 9, 18, 27, or 54 postinoculation (PI). Analysis of virus assay and serological data indicated that inoculum dose could significantly affect the pathogenesis of BCCV infection in juvenile hispid cotton rats. For example, the six animals inoculated with 3.1 or 1.1 log10 ID50-VeroE6 and euthanized on day 54 PI were virus positive and antibody positive, whereas the six animals inoculated with −0.9 or −2.9 log10 ID50-VeroE6 and euthanized on day 54 PI were virus positive but antibody negative. Microscopic examination of tissues from the animals inoculated with 3.1 or 1.1 log10 ID50-VeroE6 revealed diffuse, subacute pneumonitis in the lungs of all the animals euthanized on day 18 PI or thereafter, and indicated that the severity of pneumonitis was dependent upon inoculum dose as well as duration of infection (i.e., amount of time elapsed since inoculation)