Serologic studies of MS patients, controls, and patients with other neurologic diseases: antibodies to HTLV-I, II, III.

We have studied the frequency of human retrovirus antibody (HTLV-I, II, III) in the serum and CSF of patients with MS, matched controls, and patients with optic neuritis, idiopathic and postencephalitic Parkinson's disease, neuropathies, polymyositis, ALS, and postpoliomyelitis. Except for the postpoliomyelitis samples, all samples were collected prior to 1980. Contrary to a previous published report, no significant levels of antibody to HTLV-I, II, or III were found in the MS patients or controls. No retrovirus antibody was detected in patients with the other neurologic diseases.

Antibody to human and simian retrovirus, HTLV-I, HTLV-II, HIV, STLV-III, and SRV-I not increased in patients with multiple sclerosis.

We have tested sera from patients with multiple sclerosis, matched controls, and those with other neurological diseases, as well as sera from patients with the acquired immunodeficiency syndrome and controls and patients with tropical spastic paraparesis (TSP) and controls for antibody to human T-lymphotropic virus type I (HTLV-I), HTLV-II, human immunodeficiency virus (HIV), simian T-lymphotropic virus type III, or simian retrovirus type I by immunofluorescent activity test, and for HTLV-I and HIV by the ELISA method. Sera from patients with multiple sclerosis and matched controls, and from patients with optic neuritis and Parkinson's or other neuromuscular diseases did not have antibody to any of the retroviruses tested. Specimens from TSP patients and some controls contained HTLV-I antibody. We conclude from our study that only TSP patients had serological evidence of infection with one of the retroviruses studied.

HIV and HTLV-I antibody studies: pregnant women in the 1960s, patients with AIDS, homosexuals, and individuals with tropical spastic paraparesis.

To investigate the possible occurrence of human immunodeficiency virus (HIV) or human T-cell lymphotropic virus, type I (HTLV-I) infections in the United States prior to 1979-1981, when acquired immune deficiency syndrome (AIDS) was first recognized, we tested sera from 310 pregnant women who participated in the Collaborative Perinatal Project during the period 1959-1964 for HIV and HTLV-I antibody. These samples included sera from 53 pregnant women who were intravenous drug users. The remainder were from women who had cervical epithelial abnormalities, who developed cervical carcinomas, who had had children with erythroblastosis fetalis, who had had children that developed malignant neoplasms early in life, or normal pregnant women. None of the 310 women had confirmed HIV or HTLV-I antibody. The rate of false-positive reactions with the HIV enzyme-linked immunosorbent assay (ELISA) antibody test in these long-frozen samples was similar to that observed in fresh sera. HIV antibody was detected in homosexual patients with AIDS; HTLV-I antibody was not detected in any of these sera. HTLV-I antibody was detected in 17 of 20 patients with tropical spastic paraparesis (TSP) and in two of seven patients with other neurological diseases diagnosed as transverse myelopathy and multiple sclerosis, and in none of nine normal controls; HIV antibody was not detected in any of these sera patients. Thus, we conclude that there was no serological evidence of infection with HIV or HTLV-I in the pregnant women studied; however, HIV antibody was present in all AIDS patients tested, and HTLV-I antibody was found in the majority of patients with TSP.

Serologic studies in hairy cell leukemia: high prevalence of Epstein-Barr and cytomegalovirus antibodies and absence of human T-cell lymphotrophic viruses antibodies.

Serum from 60 patients with hairy cell leukemia (HCL) were studied for the presence and the titers of antibodies to Epstein-Barr virus (EBV), cytomegalovirus (CMV) and human T-cell lymphotrophic viruses (HTLV). Eighty-three percent of the patients were seropositive for EBV, with a (reciprocal) geometric mean titer (GMT) of 960. Seventy-eight percent of the patients had antibodies to CMV with a GMT of 435. All 21 patients tested for HTLV I and HTLV III were seronegative; only one patient showed detectable antibodies to HTLV II. The potential role of these infections in the physiopathology of HCL is discussed.

Lack of oral HSV-2 in a college student population.

A population of individuals with a high incidence of genital herpes simplex virus type 1 (HSV-1), due most likely to oro-genital contact, was examined to determine the incidence of oral herpes simplex virus type 2 (HSV-2) infection. Herpes simplex virus was isolated from the oral cavity of 43 college students whose symptoms ranged from singular lesions of the lips with minimal discomfort to severe oral disease with systemic involvement resulting in lymphadenopathy, chills, sweat, myalgia, and fever. The virus isolated from each case was identified by serum neutralization and typed as HSV-1 or HSV-2 using (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) sensitivity, monoclonal antibody immunofluorescence, and restriction endonuclease EcoRI digestion of viral DNA. In every instance the isolate was HSV-1. Additional identification and typing of head and neck isolates as well as oral samples from non-university patients demonstrated that all were also HSV-1. Therefore, while HSV-1 appears to be readily transmitted to the genitalia in this group of individuals, the transmission of HSV-2 to the oral cavity may not be as common, even though clinical histories revealed that several of these patients were engaging in oro-genital contact.

Identification and typing of herpes simplex virus types 1 and 2 by monoclonal antibodies, sensitivity to the drug (E)-5-(2-bromovinyl)-2'-deoxyuridine, and restriction endonuclease analysis of viral DNA.

With development of antiviral drugs, the need to identify a virus as to drug sensitivity becomes increasingly of importance. The compound (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) has been shown to be much more inhibitory to the replication of herpes simplex virus type 1 (HSV-1) and varicella-zoster virus as opposed to herpes simplex virus type 2 (HSV-2). We have typed over 170 isolates, using an immunofluorescent technique and sensitivity to the drug BVDU. These results were then compared to the typing of isolates by analysis of viral DNA after restriction endonuclease digestion (EcoRI). Without exception the results were in agreement between the monoclonal antibody results and sensitivity to the drug BVDU. Furthermore, the typing with monoclonal antibodies was also in excellent agreement with the DNA analysis. Only those isolates inhibited with BVDU showed DNA characteristics of HSV-1 and reacted only with the S-200 antibody. On the other hand, those isolates which reacted with the monoclonal antibody S-141 were insensitive to BVDU, and again this was in agreement with the DNA analysis. These results could provide the basis for developing a diagnostic test using the two monoclonal antibodies to type either isolates or direct smears and to use the results as a basis for possible drug therapy.

Incidence of herpes simplex virus types 1 and 2 in penile lesions of college men.

Herpes simplex virus (HSV) was isolated from penile lesions of 15 college men. Using (E)-5-(2-bromovinyl)-2'-deoxyuridine sensitivity, monoclonal antibody immunofluorescence, and restriction endonuclease EcoRI digestion of viral DNA, 4 of 15 (26%) isolates were found to be HSV-1, and 11 of 15 (74%) isolates were found to be HSV-2. It is likely that some of the genital HSV-1 infections are related to oral genital contact, but this fact could not be established for all cases, since the females in this group had previously been shown to have a high incidence of genital HSV-1.

Distribution of antibody to hepatitis A antigen in a population of commerical plasma doners.

Plasma samples from 245 regular plasma donors for Plasma Alliance, Inc. (Knoxville, Tenn.) were tested for the presence of antibody to hepatitis A antigen. Antibody was detected at an immune adherence hemagglutination titer of 1:10 or greater in 37% (91 of 245) of the donors. A statistically significant difference in the frequency of anti-hepatitis A was found between the 18- to 29-year-old group (30%) and the 30- to 49-year-old group (57%). No significant differences between whites and blacks or males afemales were observed. Eighty percent of the donors were in the age range of 18 to 29 years, whereas 48% of the higher-titered plasmas (1:1,000 or greater) were in the 30 to 49 age group. By preselection of donors, it would be possible to produce an immune serum globulin with a specific anti-hepatitis A titer.

Protective effect of immune serum globulin (ISG) against hepatitis A infection in a natural epidemic.

Serologic evidence now confirms epidemiologic evidence that human immune serum globulin (ISG) protects susceptible patients from hepatitis A provided it is administered prior to exposure to the virus. In two wards of young patients housed at the Lynchburg (Virginia) Training School and Hospital for the mentally retarded, 44 out of 60 patients had no detectable antibody to hepatitis A prior to an epidemic which took place there in 1970; 12 of 19 non-immunized susceptible patients contracted the disease, while only four of 25 patients receiving ISG developed hepatitis. These four were probably infected with the virus prior to ISG administration. Of the 16 patients with pre-existing antibody, none showed any signs of symptoms of hepatitis.

Method for extracting viral hemagglutination-inhibiting antibodies from the nonspecific inhibitors of serum.

Various methods are used to remove nonspecific inhibitors from sera before titering viral hemagglutination-inhibiting antibodies. These methods have several undesirable features; some are tedious and time-consuming, some remove antibody along with nonspecific inhibitors, and different techniques are usually required to remove the nonspecific inhibitors for different viruses. This communication describes a single method that uses diethylaminoethyl-Sephadex to extract the immunoglobulin G antibodies for several viruses from nonspecific inhibitors. The procedure is fast, simple to perform, and removed the nonspecific inhibitors for influenza, Western equine encephalitis, dengue-2, and rubella viruses.