The necessary involvement of both complementary strands of DNA in the specification of messenger RNA. Biochem. Biophys. Res. Commun. 7:471-476. 101. SWARTZ, M. N., T. A. TRAUTNER, AND A. KORNBERG. 1962. Enzymatic synthesis of deoxyribonucleic acid. XI. Further studies on nearest neighbour base sequences in deoxyribonucleic acids.

SUMMARYQuantitative studies were made of the infection of mouse peritoneal macrophages in vitro by cytomegalovirus, using virus assays and immunofluorescence. The efficiency of infection was low. Broth-induced peritoneal macrophages were about /'our times more resistant to infection than unstimulated macrophages and it was even more difficult to infect activated macrophages taken from mice 6 days after intravenous infection. Peritoneal macrophages (unstimulated) were infected at least 15 times more readily by tissue culture-passed (attenuated) virus than by salivary gland (virulent) virus, but macrophages prevented the spread of tissue culture virus to underlying susceptible mouse embryo fibroblasts, whereas they did so much less effectively with virulent salivary gland virus.The pathogenesis of infection was studied in intact mice by immunofluorescence, and the observations paralleled the in vitro findings. When large doses of salivary gland virus were injected intravenously, infected Kupffer cells (liver macrophages) were occasionally seen and the inoculated virus directly infected large numbers of hepatic cells. In similar experiments with tissue culture-passed virus, there was initial infection of occasional Kupffer cells, which only rarely gave rise to infected hepatic cells. Differences in the extent of Kupffer cell infection by the two strains of virus were not detected in these experiments. Salivary gland virus also usually failed to infect splenic or lymph node macrophages. Occasional infected mononuclear cells were seen in the blood, lung and bone marrow, but were not identified. Infected cells were very rarely seen in the thymus, even in suckling mice.

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Mouse peritoneal and alveolar macrophages differed substantially in their response to influenza in vitro. Immunofluorescent and infectious-center techniques showed that viral proteins were produced in only a small subpopulation (17%) of peritoneal macrophages and that these infected cells were removed from culture by 3 days postinfection. In contrast, alveolar macrophages were highly susceptible to influenza, and viral antigens were produced in all cells. This was accompanied by a cytopathic effect and cell death. However, no infectious virus was released and the infection was considered abortive. With mouse cytomegalovirus, however, both alveolar and peritoneal macrophages were equally restrictive, and viral antigens were produced in only 1 to 5% of either cell population. No significant differences were observed between mouse-virulent and -avirulent strains of influenza in their interaction with macrophages either in vitro or in vivo. In vivo, both strains induced an influx of cells to the alveolar spaces by 3 to 4 days postinfection, and this was reflected by a 5to 10-fold increase in the number of "macrophages" in harvest fluids at this time. Many of these cells had an altered morphology compared with alveolar macrophages from uninfected mice, and the cell population as a whole was not susceptible to influenza. However, this resistance was lost by 7 days of in vitro culture.

Retrospective comparisons of the prevalence and age, where appropriate, of some childhood infectious illnesses and vaccinations, together with serological evidence for exposure to 16 viruses, many of which have previously been implicated in the aetiology of multiple sclerosis (MS) were made in 177 patients with acute optic neuritis, other recent isolated demyelinating episodes or established MS and 164 controls. The expected high frequency of HLA-DR2 in patients with demyelinating disease was matched by preselection of normal controls with this antigen (DR2+); the remaining individuals were classified as HLA-DR2 negative/DR3 positive (DR3+) or HLA-DR2 and 3 negative (DR2/3 -). Cases were compared with controls, collectively and in analyses restricted to each genetic group; these comparisons were repeated considering the three categories of patients with demyelination and two control populations separately. All DR2+, DR3+ and DR2/3 - individuals were compared in a single analysis to assess the effect of HLA type itself on the results. Patients with demyelinating disease had rubella and measles at a later age and reported mumps infection more frequently than controls. Age of typhoid vaccination and duration of exposure to domestic dogs was higher in all cases than controls. Age of measles and mumps, but not rubella, was higher in DR2+ cases than controls; but differences were not observed in the other genetic groups. Higher rubella antibody titres were present in all cases than controls and in analyses confined to DR2+ individuals in whom higher Epstein Barr virus antibody titres were also present. Measles haemagglutination inhibition and parainfluenza I antibody titres were increased and influenza A antibodies detected less frequently in all patients with optic neuritis and those with DR2 compared with appropriate controls; influenza B antibody titres were lower in all DR2+ cases than controls. Higher adenovirus and varicella zoster antibody titres were present in DR2/3- patients with demyelination and other neurological diseases compared with normal controls. Overall, older age of infection and higher antibody titres were observed more often in patients with optic neuritis, in particular DR2+ cases, than other individuals with demyelination or controls. Our serological results are consistent with the presence of abnormal HLA-immunological reactivity in patients with MS but cannot be explained only by an effect of DR type itself; age at which susceptible individuals develop some common childhood infections may also influence the subsequent development of the disease.