Single doses of TNX-355 reduced plasma HIV-1 RNA loads and increased CD4+ T cell counts in HIV-infected subjects. The further assessment of therapeutic potential awaits data from longer-duration trials.

No abstract

The infectivity titer of a standard stock of the SAR-55 strain of hepatitis E virus (HEV) was determined in cynomolgus macaques (Macaca fascicularis) and the effect of dose on the course of the infection was examined by weekly monitoring of alanine aminotransferase (ALT) and anti-HEV levels. Antibody to HEV (anti-HEV) was measured with ELISAs based on ORF-2 recombinant antigens consisting of either a 55 kDa region expressed in insect cells or shorter regions expressed as fusion proteins in bacteria. The ELISA based on the 55 kDa antigen was generally more sensitive. The infectivity titer of SAR-55 was 10(6) cynomolgus 50% infectious doses per gram of feces. The infectivity titer corresponded to the HEV genome titer of the inoculum as determined by reverse transcriptase-polymerase chain reaction (RT-PCR). Anti-HEV IgM was detected in only a portion of the animals that had an anti-HEV IgG response. Biochemical evidence of hepatitis was most prominent in animals that were inoculated with the higher concentrations of virus and the incubation period to seroconversion was prolonged in animals that received the lower doses.

If the occurrence of hepatitis E virus antibody (anti-HEV) in regions where the disease is not endemic represents infection, rates may be greater in high-risk populations and behavioral correlates may reflect recognized transmission modes. Serum samples from 300 homosexual males, 300 injection drug users (IDUs), and 300 blood donors from Baltimore, Md., were tested for anti-HEV by enzyme immunoassay. Anti-HEV was found in an unexpectedly high percentage of homosexual men (15.9%) and IDUs (23.0%). However, anti-HEV was present in a similar proportion of blood donors (21.3%) (P > 0.05), while hepatitis A, B, and C virus antibodies were more prevalent in the high-risk groups (P < 0.001). Among homosexual men, anti-HEV was not significantly correlated with a history of hepatitis, high-risk sexual practices, or sexually transmitted infections, in contrast to hepatitis A and B antibodies. Among IDUs, anti-HEV was not significantly associated with a history of hepatitis or high-risk drug-using practices, as was found with hepatitis C antibodies. In a setting without endemic hepatitis E disease, there was no evidence that anti-HEV reflected subclinical infection. Until the basis for HEV seroreactivity in such areas is elucidated, anti-HEV results should be interpreted with caution.

Large epidemic outbreaks of enterically transmitted non-A, non-B viral hepatitis (ET-NANBH) have been documented in developing countries. A molecular clone derived from the causative agent, the hepatitis E virus (HEV), has recently been described (G.R. Reyes, M.A. Purdy, J.P. Kim, K.-C. Luk, L.M. Young, K.E. Fry, and D. Bradley, Science 247:1335-1339, 1990). We now report the isolation, by serologic screening, of two cDNA clones derived from a fecal sample collected during a 1986 outbreak of ET-NANBH in Telixtac, Mexico. The cDNA clones encode epitopes that specifically reacted with acute- and convalescent-phase sera collected during five different ET-NANBH epidemics and represent the initial cloning of the Mexico strain of HEV. Recombinant fusion proteins expressed from these clones were also recognized by antibodies from cynomolgus macaques experimentally infected with HEV. The cDNA clones were shown to be derived from HEV by their specific hybridization to the previously recognized full-length genomic RNA transcript of approximately 7.5 kb. In addition, however, subgenomic polyadenylated transcripts of approximately 2.0 and approximately 3.7 kb were also identified in HEV-infected cynomolgus monkey liver. Sequences homologous to the epitope clones were isolated from the Burma strain of the virus, and these demonstrated reactivity comparable to that seen with the Mexico strain epitopes. When compared with the available full-length sequence of the Burma strain of HEV, it was discovered that the cDNA clones were encoded in different open reading frames (ORFs). The comparison between Mexico and Burma HEV strains indicated amino acid homologies of 90.5 and 73.5% for these epitope-encoding clones derived from ORF2 and ORF3, respectively. The identification of these clones not only has provided insight into the expression strategy of HEV but has also resulted in a source of recombinant protein useful in the diagnosis of HEV-induced hepatitis.