Charles A. Daniels

Depressed monocyte chemotaxis during acute influenza infection.

The chemotactic responsiveness of monocytes from patients with serologically proven influenza infection has been quantified in vitro. Individuals with acute influenza had a significant (P less than 0-001) depression of monocyte chemotaxis. The depression ranged from 40% to 72% during acute infection but rose to normal by three weeks after recovery. When isolated mononuclear leucocytes from the recovered patients were incubated with the infecting strain of virus (Port Chalmers), a 49-54% inhibition of chemotaxis was obtained. These findings support the hypothesis that the altered immune responsiveness and increased predisposition to superinfections found frequently in patients with influenza can be due to the ability of the virus to depress monocyte function.

Neutralization of sensitized virus by the fourth component of complement.

Herpes simplex virus which had been sensitized with IgM antibody was not neutralized by the addition of the purified activated first component of complement. In the presence of an optimum concentration of the first component of complement, however, the sensitized virus was neutralized by the addition of a high concentration of the purified fourth component of complement. Under these conditions, the addition of the purified second and third components of complement failed to enhance virus neutralization. With low concentrations of the fourth component of complement, the addition of the second and third components enhanced virus neutralization.

Interaction of Rheumatoid Factor with Infectious Herpes Simplex Virus-Antibody Complexes

Rheumatoid factor, a human immunoglobulin of the IgM class, failed to attach to herpes simplex virus but did attach to infectious complexes composed of herpes simplex virus and antibody to herpes simplex virus. These newly formed complexes of infectious virus, antiviral antibody, and rheumatoid factor could be neutralized by complement or by antibody to human IgM. The ability of rheumatoid factor to enhance virus neutralization in the presence of complement represents a hitherto unrecognized biological role for rheumatoid factor.

Shedding of infectious virus/antibody complexes from vesicular lesions of patients with recurrent herpes labialis.

The concentration of herpes-simplex virus (H.S.V.) in the lesions of adults with recurrent herpes labialis was determined. On the 1st day the vesicle appeared, the fluid within the lesion contained 10(5-3) plaque-forming units (P.F.U.) of H.S.V./mul. By swabbing the surface of the lesions with a sterile pledget, 10(6-2) P.F.U. of virus was isolated from the inflamed labial mucosa. The amount of virus obtained from the labial surface decreased on the 2nd and 3rd day to 10(5-0) and 10(3-0) P.F.U., respectively. In two patients on immunosuppressive drugs, high concentrations of virus (greater than 10(4-0) P.F.U.) were obtained per swab for more than 3 weeks. The presence of infectious virus-antibody (V.A.) complexes in herpetic lesions was demonstrated by examining fifty-two isolates from twenty-eight patients at various times during the course of their disease. 71% of the patients had V.A. complexes in their lesions on the 1st day of the vesicular eruption, and by the 3rd day all of the lesions examined contained complexes. It is concluded that patients with active lesions shed high concentrations of virus and that natural infection may be transmitted by an infectious V.A. complex.

Influenza-induced depression of monocyte chemotaxis: Reversal by levamisole☆

Abstract Depression of monocyte chemotactic responsiveness that occurs in patients with acute influenza may be a factor in causing the high incidence of superinfection seen in this viral disease. Levamisole, a pharmacological agent capable of enhancing monocyte chemotaxis, was effective in counteracting the depression of chemotaxis produced by incubating normal monocytes with influenza in vitro . The drug, moreover, enhanced the subnormal in vitro chemotactic responses of monocytes from patients with serologically proven acute influenza. These studies suggest that levamisole may be useful in enhancing depressed cellular immune function in patients with acute influenza.

MECHANISMS OF VIRAL NEUTRALIZATION

Publisher Summary This chapter discusses the mechanisms of viral neutralization. Neutralization is the loss of virus infectivity caused by antibody. The attachment of one antibody molecule to a native virus is insufficient to cause neutralization. Instead, many immunoglobulin molecules must bind to the surface to render the virus noninfectious. There are at least three mechanisms of neutralization: (1) coating of the virus surface, (2) aggregation of particles, and (3) virolysis. Antibody alone can coat or aggregate, but complement may cause all three of these mechanisms of neutralization to take place. Out of these, the one mechanism that occurs in vitro in a given situation depends on the relative abundance of the virus, antibody, and complement as well as the type of virus and antibody involved. The in vivo importance of the various mechanisms of virus neutralization remains to be determined. Whether an antibody neutralizes a virus depends on the site of attachment and physiochemical properties of the binding immunoglobulin. It can be assumed that these parameters would also be important in the neutralization of infectious virus–antibody complexes by accessory factors.

Growth of type 2 herpes simplex virus in newborn and adult mononuclear leukocytes.

Growth of type 2 herpes simplex virus (HSV) in newborn and adult human mononuclear leukocytes (MNL) was compared. Phytohemagglutinin stimulation of cultures for 3 days yielded comparable peak titers in newborn (10(5.3) PFU) and adult (10(5.1) PFU) MNL. Unexpectedly, 3-day cultures of unstimulated newborn MNL also substantially replicated HSV (10(4.7) PFU), whereas similarly treated unstimulated adult cells did not. Growth of HSV in freshly isolated human MNL was next investigated. MNL from 4 mothers and 6 nonpregnant adults showed no evidence of virus growth; however, leukocytes from 11 of 24 newborns (46%) supported replication. Newborn MNL manifested an increased ability to replicate HSV within 1 day of culture, whereas comparable growth in adult MNL was not achieved until the 4th day of culture. The significance of the above observations as it relates to visceral dissemination of HSV in the neonate is discussed.

The effect of rheumatoid factor on the immune lysis of vaccinia virus-infected cells☆☆☆

Abstract Monolayers of mouse embryo fibroblasts were labeled with 51 Cr and infected with vaccinia virus. When sequentially incubated with rabbit antivaccinial antibody and excess guinea pig complement, the fibroblasts lysed and liberated 51 Cr into the medium. The 51 Cr released was proportional to the antiviral antibody concentration incubated with the cells. When the infected cells were treated with antibody and exposed to 125 I-labeled human rheumatoid factor (RF), the labeled antiglobulin bound to the antiviral antibody on the virus-infected cells. The effect of RF and goat anti-rabbit IgG on complement-mediated lysis was determined. When high concentrations of antiviral antibody were incubated with the infected cells both RF and anti-rabbit IgG inhibited complement-mediated cytolysis. At low concentration of antibody, RF had no effect on immune lysis, while anti-rabbit IgG enhanced lysis. This is a hitherto unrecognized role of RF and suggests that RF in vivo may alter the humorally mediated immune cytolysis of virus-infected cells.