Experimental infection of marmosets with hepatitis A virus.

Saguinus mystax marmosets were experimentally infected with two strains of human hepatitis A virus. One of these strains of HAV was successfully subpassaged in this species of marmosets. In another experiment, the 1.32 and 1.41 g/cm3 buoyant density species of HAV derived from an infected chimpanzee stool were shown to be infectious in three species of marmosets. The value of the marmoset as an experimental model for hepatitis A infection was demonstrated by these studies.

Hepatitis B virus infection in chimpanzees: titration of subtypes.

Thirty-four chimpanzees were inoculated with sera containing the adw, ayw, adr, or ayr subtype of hepatitis B surface antigen (HBs Ag). Twenty-nine of the animals became infected with hepatitis B virus, and in every instance the subtype of HBs Ag in the infected animal was the same as the subtype in the inoculum. Infectivity titers were established for the adw and ayw inocula. The patterns of serologic events varied in the infected animals but included most of the typical patterns of serologic change seen in human cases of type B hepatitis. Mild disease, manifested by elevated concentrations of serum enzymes and changes detected by liver biopsy, occurred in 23 of the 29 infected animals.

Review of infectivity studies in nonhuman primates with virus-like particles associated with MS-1 hepatitis.

Using the technique of immune electron microscopy we have conducted hepatitis A infectivity studies in marmoset monkeys and chimpanzees. Marmosets inoculated with human serum containing the MS-1 strain of hepatitis A virus have developed hepatitis and seroconverted to 27 nm virus-like particles isolated from stools of humans in the early acute stages of hepatitis. Similar results have been observed through several marmoset subpassages, and the virus-like particles have been recovered from the liver of animals in the acute phase of hepatitis. Chimpanzees inoculated with stool filtrates containing the virus-like particles develop hepatitis with concomitant excretion of the particles in early acute phase stools and subsequent development of serum antibody to the particles. These studies provide evidence that the above particles constitute the virus of hepatitis A of the MS-1 prototype.

Effect of penicillin on the humoral and cellular immune response following group A streptococcal pharyngitis.

The effect of oral and parenteral penicillin on the development of cellular and humoral immune responses in chimpanzees infected with group A streptococcal M-types 1, 5 and 12 was investigated. The interrelationship between type-specific antibody response and enhancement of phagocytic competence of polymorphonuclear neutrophils was documented. Penicillin depressed or suppressed type-specific antibody response depending on the mode and dose of administration, probably because of its effect on the streptococci responsible for antibody stimulation. Penicillin was not demonstrated to have a direct effect on phagocytic ability in vitro. Therefore the primary effect of antibiotic therapy is the indirect relationship to suppression or inhibition of type-specific antibody response to M-protein which results in a diminution of phagocytic competence.

Infectivity studies of hepatitis A and B in non-human primates.

We have induced hepatitis A in marmosets of the subspecies Saguinus mystax following primary inoculation with human serum containing the MS-1 strain of hepatitis A virus (HAV) and in 3 further marmoset subpassages using infective marmoset serum from each preceding passage. In each passage acquisition of serum antibody against 17 nm virus-like particles recovered from acute illness stools of human volunteers who developed hepatitis following inoculation with the MS-1 strain of HAV, as well as from acute illness stools of hepatitis A cases from a common source epidemic of heaptitis A in Arizona could be demonstrated by immune electron microscopy (IEM). Particle-containing stool filtrates from the latter epidemic also induced hepatitis in chimpanzees after intravenous inoculation. Inoculation of partially purified particles from a single banding in CsCl2 has further resulted in the induction of hepatitis in S. mystax marmosets. We have successfully induced hepatitis in a series of chimpanzees inoculated with sera containing hepatitis B surface antigen (HBsAg) of varying subspecificities. Susceptibility appears universal in animals who are initially lacking in serum antibody (anti-HBs) and antibody induced following experimental infection is homologous in subspecificity to the subspecificities of the antigenic coat components of the HBsAg in the inoculum. Results of cross challenge experiments indicate that animals developing hepatitis following inoculation of HBsAg of one subspecificity set in the d/y-w/r system do not again develop hepatitis following inoculation with HBsAg of the alternate subspecificity set.

Occurrence of a carrier state for Herpesvirus tamarinus in Marmosets.

The ecology of herpesviruses in marmosets and other nonhuman primates is important today, for colonies of these animals are being established for biomedical research. This paper presents the first reported isolations of Herpesvirus tamarinus from throat swabs of a healthy white-lipped marmoset carrier (Saguinus nigricollis) during a 2-month period. Infectivity studies with this virus in both white-moustached (S. mystax) and white-lipped marmosets demonstrated that the virus is not lethal to white-moustached marmosets (perhaps a more resistant species) at 1,000 TCID(50). Which environmental conditions trigger the unmasking of herpesviruses in marmosets is not known. Hoever, intermittent H. tamarinus shedding may help explain spontaneous infections in established colonies as well as suggest an additional mechanism for transmission of virus between marmosets under natural conditions.