No abstract

Inoculation of human serums or plasmas obtained during the early acute phase of viral hepatitis induced chemical and morphological hepatic disease in marmosets in two out of five experimental series. The disease was transmissible in series from marmoset to marmoset with an apparent increased virulence of the causative agent in later marmoset passages. The chemical evidence for the disease was elevation of the activity of SGOT and SICD and of serum bilirubin. In serial liver biopsy specimens interpreted under code, a hepatitis, exhibiting some of the characteristics of human viral hepatitis, was readily distinguishable from nonspecific changes. The morphological changes preceded the biochemical alterations and persisted after them. The data reported in these studies indicate that marmosets may be susceptible to human hepatitis. If these observations are confirmed, these animals may provide good experimental models for this disease. Final proof that the hepatitis observed in marmosets is caused by agents of human viral hepatitis is still lacking.

A 13-day-old lowland gorilla died from a generalized herpesvirus infection shortly after the onset of clinical signs. The pathologic-anatomical findings were compatible with those described for generalized herpes simplex infection in the human neonate. Electron microscopic examination of lung tissue revealded the presence of herpesvirus which was identified with the fluorescent antibody technique as Herpes simplex virus type 1. Tests with related sera of the herpes group (varicella, herpesvirus-B) revealed no specific immunofluorescence.

Infectious cellular uptake of human immunodeficiency virus (HIV) is initiated by a complex sequence of interactions between the viral envelope gp120/gp41 complex and the cellular CD4 receptor resulting in the exposure of a hydrophobic region of gp41 that mediates the irreversible fusion of the virus with the cell membrane. Here we show that viral penetration into a susceptible cell can be inhibited by the high-affinity monoclonal CD4 antibody (CD4 mAb) M-T413 even when it is added as late as 30-120 min after the initial contact of virus with the cell membrane. Inhibition of infection was assessed by monitoring cultures for 34 days after exposure to virus using four different methods simultaneously, including detection of viral DNA by PCR. The interval during which HIV remains sensitive to postbinding neutralization by CD4 mAb depends on strain of virus and type of target cell. Preparations of recombinant soluble CD4 (and the immunoadhesin CD4-IgG1) were much less efficient when compared with mAb M-T413, particularly in blocking infection by fresh HIV-1 isolates. Also cellular transmission of HIV, as determined by syncytia formation within 24 hr, was prevented by mAb M-T413 when added within 45 min of contact of infected H9 cells with uninfected C8166 cells. Together with the favorable clinical experience obtained with CD4 mAbs as immunomodulatory drugs, these data suggest that infusion of CD4 mAb M-T413 may be a therapeutic modus for immediate prophylactic intervention after occupational exposure to HIV and for prevention of intrapartum mother-to-infant HIV transmission.