Chanock, and B

Chanock, and B. protection. Both HMPV strains replicated to low titers in the upper and lower respiratory tracts of rhesus macaques but induced high levels of HMPV-neutralizing antibodies in serum effective against both lineages. The level of HMPV replication in chimpanzees was moderately higher, and infected animals developed moderate colds. HMPV replicated the most efficiently in the respiratory tracts of African green monkeys, and the infected animals developed a high level of HMPV serum-neutralizing antibodies (1:500 to 1 1:1,000) effective against both lineages. Reciprocal cross-neutralization assays in which postinfection sera from all three primate species were used indicated that CAN75 and CAN83 are 64 to 4-Hydroxytamoxifen 99% related antigenically. HMPV-infected chimpanzees and African green monkeys were highly guarded from challenge with the heterologous HMPV strain. Taken together, the results from hamsters and nonhuman primates support the conclusion that the two HMPV genetic lineages are highly related antigenically and are not distinct antigenic subtypes or subgroups as defined by reciprocal cross-neutralization in vitro. Human metapneumovirus (HMPV), which was first identified several years ago in The Netherlands (39), is usually a member of the family and has been tentatively assigned to the genus of the subfamily. This subfamily also includes the genus, made up of the respiratory syncytial computer virus (RSV). Since its initial discovery, HMPV has been found to infect humans worldwide (7, 29, 31). Extensive sequence analysis of isolates from around the world indicates 4-Hydroxytamoxifen that there are two major genetic lineages of HMPV (3). It has been suggested that the different HMPV lineages represent different HMPV serotypes (29, 40). However, the biology and epidemiology of the newly identified HMPVs are not well characterized. Mouse monoclonal to EphB6 For example, the overall impact of HMPV disease on hospitalization for respiratory tract disease is not well established, and it is not known if contamination with one HMPV genetic lineage can induce protective immunity against reinfection with homologous or heterologous HMPV strains. Moreover, the lack of established animal models of HMPV replication and the reportedly poor growth characteristics of this computer virus have impeded its characterization. Like all members of the family, HMPV is an enveloped single-stranded negative-sense RNA computer virus. The genome is usually approximately 13 kb in length, and the HMPV 3-to-5 gene order is usually N-P-M-F-M2-1/M2-2-SH-G-L, which is the same as that of the avian members 4-Hydroxytamoxifen of the genus (5, 38). The CAN98-75 (CAN75) and CAN97-83 (CAN83) strains of HMPV were isolated in Canada from clinical samples and represent members of each of the two major genetic lineages (31). The amino acid identity of the predicted encoded proteins between these two strains is usually 96% (N protein), 85% (P protein), 97% (M protein), 95% (F protein), 96% (M2-1 protein), 89% (M2-2 protein), 59% (SH protein), 37% (G protein), and 94% (L protein) (5). Thus, with the notable exception of the SH and G proteins, the polypeptides encoded by each of these genetic lineages are 4-Hydroxytamoxifen highly related at the amino acid level. The major question addressed in this article is usually that of the antigenic relatedness of the two strains of HMPV. The answer to this question will have implications for HMPV epidemiology and for the formulation of a strategy to develop vaccines effective against this important respiratory pathogen. We first identified suitable cell culture growth conditions to generate HMPV suspensions of sufficient titer for administration to experimental animals. It was also necessary to identify suitable small-animal and nonhuman primate models for HMPV replication. The present study demonstrates that the two HMPV lineages exhibited a high level of antigenic relatedness in rodents and nonhuman primates including chimpanzees and a high level 4-Hydroxytamoxifen of cross-protective efficacy, indicating that these two strains do not represent distinct antigenic subtypes. This study also establishes hamsters and African green monkeys as suitable animal models for HMPV replication and immunogenicity. MATERIALS AND METHODS Cell lines and viruses. Rhesus monkey kidney cells (LLC-MK2; ATCC CCL 7.1) cells were maintained in.