Paul M. Feorino

Primary Epstein–Barr-Virus Infections in Acute Neurologic Diseases

Infectious mononucleosis has been associated with Guillain--Barré syndrome, Bells palsy, meningoencephalitis and transverse myelitis. Since it is not known that many children with infectious mononucleosis do not develop heterophil antibodies, we looked for evidence of current or recent Epstein-Barr virus infection in young patients with these neurologic diseases by using serodiagnostic procedures for detection and titration of antibodies to various antigens related to Epstein-Barr virus. Seven of 24 cases with Guillain-Barre syndrome and three of 16 with facial palsy were definitely associated with primary infection with Epstein-Barr virus as were two cases each of the other two neurologic diseases. Only one of these patients had obvious clinical infectious mononucleosis, and only a few demonstrated heterophil agglutinins. It is evident that the virus must be considered in the diagnosis of various acute neurologic diseases affecting children and young adults, even in the absence of heterophil-antibody response or other signs of infectious mononucleosis.

Central-Nervous-System Lymphoma Related to Epstein–Barr Virus

We have studied five cases suggesting a relation between Epstein-Barr virus infection and primary lymphoma of the central nervous system. A 48-year-old man had primary lymphoma of the central nervous system in the absence of systemic lymphoma or immunosuppression. Development of the tumor was associated with serologic evidence suggesting a recent primary infection with Epstein-Barr virus. DNA preparations from tumor tissue, but not from adjacent normal brain tissue, contained Epstein-Barr virus genomes when hybridized with a probe consisting of the BamHI K fragment of Epstein-Barr virus strain FF41. Evaluation of serum samples from four additional patients with central-nervous-system lymphoma revealed patterns of Epstein-Barr virus-specific antibody that were suggestive of an ongoing infection with EBV. Our results suggest induction of the lymphoma by Epstein-Barr virus.

National Case-Control Study of Kaposi's Sarcoma and Pneumocystis carinii Pneumonia in Homosexual Men: Part 2, Laboratory Results

The Centers for Disease Control conducted a case-control study to investigate an outbreak of Kaposis sarcoma and Pneumocystis carinii pneumonia in homosexual men. The occurrence of these diseases was found to be associated with certain aspects of lifestyle, including a greater number of male sex partners per year, exposure to feces during sex, history of syphilis and non-B hepatitis, treatment for enteric parasites, and use of various illicit substances. Laboratory studies reflected both this lifestyle and the probable underlying cause of the Kaposis sarcoma and P. carinii pneumonia--cellular immune deficiency. Patients were found to have lymphopenia, specifically a deficiency of the T-helper subpopulation, resulting in a reversal of the T-helper to T-suppressor ratio. Levels of IgG and IgA were increased. When compared with controls, patients were also found to have significantly higher titers of antibody to Epstein-Barr virus and cytomegalovirus, a higher prevalence of antibody to hepatitis A virus and Treponema pallidum, a lower prevalence of antibody to varicella zoster virus, and a higher frequency of isolation of cytomegalovirus.

Kawasaki Syndrome: Description of Two Outbreaks in the United States

Investigation of two outbreaks of Kawasaki syndrome (KS) in the United States in 1979 and in 1980 revealed no evidence of person-to-person transmission or of a common-source exposure among patients. Questionnaire data showed that KS was more likely to occur in children of middle and upper socioeconomic status than in those of lower status (P less than 0.05 and P less than 0.001 for the respective outbreaks) and that patients with KS had a higher incidence of an antecedent, primarily respiratory illness than did controls matched for age, sex, and race (83% of patients in the first outbreak vs. 30% of one control group, P less than 0.01, and vs. 36% of another control group, P less than 0.02; and 56% of patients in the second outbreak vs. 32% of their controls, P less than 0.02). However, laboratory studies did not identify an etiologic agent for either KS or for the antecedent illness that may be a risk factor for KS.

Transfusion-associated acquired immunodeficiency syndrome. Evidence for persistent infection in blood donors.

To investigate whether infection with human T-cell lymphotropic virus/lymphadenopathy-associated virus (HTLV-III/LAV) may be persistent in asymptomatic persons and to correlate infection with seropositivity the authors performed virologic and serologic studies in 25 of 30 persons who were identified as being at high risk for the acquired immunodeficiency syndrome (AIDS) and who had donated blood to patients who later contracted transfusion-associated AIDS. High-risk donors were those who belonged to a high-risk population had AIDS or a closely related condition or had a low ratio of helper to suppressor T lymphocytes. The authors performed similar studies in 6 of the 24 patients with AIDS who had received donations from this group. HTLV-III/LAV was isolated from 22 of the 25 donors between 12 and 52 months (mean 28) after they had donated blood and from all 6 recipients between 14 and 37 months (mean 26) after they had received blood. Of the 22 virus-positive donors 2 have contracted AIDS 5 have generalized lymphadenopathy and 15 (68%) remain asymptomatic. Antibodies to HTLV-III/LAV were detectable by the enzyme-linked immunosorbent assay in serum samples obtained from each person at the time the virus was isolated. It is concluded that infection with HTLV-III/LAV may be persistent and asymptomatic for years. This demonstrates that viremic patients may be asymptomatic supports the use of serologic screening of donated blood to supplement current procedures for the prevention of transfusion-associated AIDS. (authors)

Molecular characterization of human immunodeficiency virus from Zaire: nucleotide sequence analysis identifies conserved and variable domains in the envelope gene.

To examine the genetic relatedness of human immunodeficiency viruses (HIV) from different geographic locations, we molecularly cloned the genome of HIV isolated from a Zairian AIDS patient. Restriction mapping of the recombinant clone, designated HIV-Zr6, revealed both common (as observed in other HIV isolates) and unique restriction sites. The DNA clone of HIV-Zr6, shown to give rise to infectious cytopathic virus after transfection of cultured lymphoid cells, was sequenced in several regions. The long terminal repeat (LTR), open reading frame 1 (ORF1), C-terminal envelope (env) gene domain, and ORF2 showed less than 6% difference in nucleotide sequence when compared to other HIV isolates including human T-lymphotropic virus-type III (HTLV-III) clone B10, lymphadenopathy-associated virus-1 (LAV-1), and AIDS-associated retrovirus-2 (ARV-2). About 15% difference in nucleotide sequences was noted in the N-terminal env gene domain. Alignments of env gene sequences revealed conserved, moderately variable, and hypervariable stretches in the predicted amino acid sequences. This model provides a basis for assessing the significance of sequence variation on properties controlled by the viral Env glycoproteins such as cell tropism and immunogenicity.

Possible Female-to-Female Transmission of Human Immunodeficiency Virus

Excerpt To the editor: A case of the acquired immunodeficiency syndrome (AIDS) in a lesbian without any recognized risk factors was reported in 1984 (1). Consistent with that observation, we report...

Persistent Infection with Human T-Lymphotropic Virus Type III/Lymphadenopathy-Associated Virus in Apparently Healthy Homosexual Men

A group of 14 apparently health homosexual men with serologic evidence of human T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) infection were studied to determine the duration of their seropositivity, their immunologic status, and the frequency of isolation of HTLV-III/LAV from their peripheral blood. The men were selected from a larger sample of patients who attended a clinic for treatment of sexually transmitted diseases in San Francisco because they did not have acquired immunodeficiency syndrome (AIDS), signs or symptoms suggestive of the prodrome of AIDS, or laboratory evidence of anemia or leukopenia. 4 or more serum samples were available from previous clinic visits. The men ranged in age from 26-41 years, and had a median number of sexual partners in the last year of 23. The estimated duration of seropositivity ranged from 4-69 months (median, 33 months). 11 of the 14 had T-helper: T-suppressor cell ratios below 1 (the lower limit of normal), and low ratios were significantly correlated with duration of seropositivity. HTLV-III/LAV was isolated in peripheral blood samples from 8 of 12 men tested. Culture-positive and culture-negative men did not differ significantly in terms of age, presence of a palpable lymph node, T helper:T-suppressor cell ratio, or duration of seropositivity. These findings suggest that some seropositive men may remain asymptomatic for at least 5 years. However, the isolation of HTLV-III/LAV from the peripheral blood of most of these men indicates persistent infection may be common among asymptomatic seropositive men at risk for AIDS. It should be assumed that these men have the potential to transmit HTLV-III/LAV infection.

Herpes simplex virus type 2 and cancer of the prostate.

A seroepidemiologic study was performed to determine if there was an association between antibodies to herpes simplex virus type 2 and cancer of the prostate, similar to that reported for herpes simplex virus type 2 and cervical carcinoma. No significant difference in herpes simplex virus type 2 antibodies was seen between patients with cancer of the prostate and those with benign prostatic hypertrophy. Further studies are needed to define the possible role of herpes simplex virus type 2 in the etiology of cancer of the prostate.

Genomic Heterogeneity of Human Herpesvirus 6 Isolates

Human herpesvirus 6 (HHV-6) is the causative agent of the mild childhood disease exanthem subitum (1). Its role in adult disease and in more severe disease of children has not been defined, although preliminary studies have found evidence for changes in HHV-6 serologic status in association with episodes of mild, afebrile illness presenting with symmetrical lymphadenopathy (2). Viral DNA sequences have been found in B-cell lymphoma tissue (3) and cervical lymph nodes of normal individuals (4). HHV-6 has been isolated from people of several continents (1, 5–10). Seroprevalence studies indicate that most individuals have been infected (11–15) and that initial exposure to the virus occurs early in life (1, 11, 13, 14). The route or routes of infection have not been defined. Acquisition via breast milk has not been ruled out, but it is clear that another route of transmission must exist (16). The question of whether an individual can be infected by multiple strains of the virus has not been studied.