Syrian hamsters, strain MHA/Lak, are susceptible to intraperitoneal infection with Pichinde virus and die from an overwhelming viremia. We have studied the ability of a vaccinia-Pichinde recombinant virus expressing amino acids 51-561 of the viral nucleoprotein (VVNP51-561) to protect from lethal Pichinde virus infection. Priming with VVNP51-561 significantly delayed mortality and increased final survival outcome after challenge with 2×103 pfu of Pichinde virus. This protection was not complete compared to priming with Pichinde virus in the footpad, which was not lethal and provided 100% protection. At a higher challenge dose of Pichinde virus, 2×104 pfu, immunization with VVNP51-561 delayed mortality but did not increase final survival. The partial protection correlated with an early but not late reduction in infectious virus in serum, kidney and liver, and infectious centers in the spleen. Thus the immune response generated by VVNP51-561 could initially control the infection, effectively reducing the virus inoculum. As the infection proceeded, virus replication could not be limited resulting in death in some hamsters. The partial protection did not appear to be mediated by anti-viral antibodies since these were not detected in the serum of VVNP56-561-immunized hamsters. This finding appears to support the hypothesis that in many arenavirus infections cellular immunity is central to viral clearance and protection from reinfection.

This study shows that 10% of Panamanian women are infected with VPH. This incidence of premalign and malign infection is one of the highest in the world. It is necessary that panamanian women be educated to participate in the program of the early detection of the disease to control the incidence of cancer in the uterine cervix.

A case‐control study of 766 histologically confirmed incident cases of invasive cervical cancer and 1,532 hospital and community controls was conducted in Latin America to evaluate the etiologic role of herpes simplex virus type 2 (HSV‐2) and to examine whether HSV‐2 interacts with other risk factors. In addition to a personal interview, all subjects were asked to donate blood samples and cervical swabs for assessment of exposure to HSV‐2 and human papillomaviruses (HPVs) respectively. Ninety‐eight percent of cases and 91% of controls agreed to the interview and blood collection. Women testing positive for HSV‐2 antibodies were found to have a 60% increased risk of cervical cancer compared with seronegative women (95% CI = 1.3, 1.9). Control for education, sexual and reproductive behavior, prior Pap‐smear screening, smoking, oral contraceptive use, HPV‐6/11 DNA, or HPV‐16/18 DNA detection did not materially affect this estimate. No effect modification of HSV‐2 by age, HPV‐6/11 DNA, pregnancies, oral contraceptive use or cigarette smoking was observed. However, a significant interaction was detected between HSV‐2 and HPV‐16/18. Compared with women testing negative to both virus types, those positive for HSV‐2 alone had a RR of 1.2 (95% CI = 0.9, 1.6), those positive for HPV‐16/18 DNA alone had a RR of 4.3 (95% CI = 3.0,6.0), and those positive for both viruses had a RR of 8.8 (95% CI = 5.9, 13.0). These findings corroborate recent laboratory evidence of a possible biological interaction between HSV‐2 and HPV‐16/18 in the development of cervical cancer. Further confirmatory studies are needed, given concerns with potential misclassification of exposure by the laboratory assays utilized.

Pichinde virus (PV) infection of mice results in induction of a strong H-2 restricted, virus-specific cytotoxic T lymphocyte (CTL) response and rapid clearance of the virus. To define the specificities of CTL induced by PV infection, we constructed vaccinia virus recombinants containing cloned cDNAs corresponding to full-length (VVNP) and a truncated form (VVNP51–561) of the nucleoprotein (NP) gene of PV. Radioimmunoprecipitation analysis of infected cell lysates indicated that VVNP expressed a PV-specific product identical in size to that of authentic NP, while vaccinia virus recombinants containing truncated NP produced a polypeptide consistent with the synthesis of amino acids 51–561 of Pichinde virus NP. Interestingly, cells infected with VVNP synthesized easily detectable, but much lower levels of nucleoprotein relative to both PV and VVNP51–561. Primary virus-specific CTL induced in three different strains of inbred mice following intravenous infection with PV were able to lyse syngeneic target cells infected with PV but did not markedly lyse syngeneic targets expressing full-length or truncated NP following recombinant vaccinia virus infection. Similarly, secondary anti-PV specific CTL generated following in vitro restimulation by PV or selectively restimulated with vaccinia recombinants did not significantly lyse target cells expressing NP. Further, infection of mice with VVNP and VVNP51–561 did not induce CTLs specific for PV and did not prime mice for the generation of memory anti-PV CTL in vivo. These results suggest that PV gene products other than NP, such as the GPC or L protein, contain the major target epitope(s) recognized by PV-specific CTL.

A study of 759 cervical cancer patients, 1,430 controls, and 689 sex partners in four Latin American countries has made it possible to assess the influence of multiple factors upon the risk of invasive cervical cancer. The principal risk factors identified were the woman's age at first coitus, the number of her steady sex partners, her number of live births, the presence of DNA from human papillomavirus (HPV) types 16 or 18, a history of venereal disease, nonparticipation in early detection programs, and low socioeconomic status. There is good reason to believe that extensive detection programs directed mainly at high-risk groups in the Americas can reduce the high incidence of cervical cancer in this Region.

A population-based national cancer registry has documented strikingly different regional incidence rates of cervical cancer in the Republic of Panama. Such regional differences in disease rates could represent regional differences in the occurrence of risk factors, in particular, human genital papillomaviruses (HPV). This study enrolled newly diagnosed invasive cancer patients in the Republic of Panama over an 18-mo period. Behavioral risk factors were measured by interviewing cases and matched controls. In addition, DNA extracted from biopsies of the cancers was tested for HPV sequences. Early age at first coitus, multiple pregnancies, and nonparticipation in Pap smear screening programs were significant risk factors for cervical cancer in this population. These factors and low levels of education occurred more frequently among women residing in regions with higher cancer rates than women residing in the region with lower cancer rates. HPV DNA was detected most frequently (70%) among cases from the region with the lowest cancer rate (30 of 100,000) and least frequent (54%) among cases where the cancer rate was the highest (51 of 100,000). The observations suggest that risk factors other than HPV contribute to the differences in cervical cancer rates among women residing in various regions of Panama.

The role of viruses in the induction of papillomas which may persist and give rise to malignant lesions was demonstrated in animals a number of years ago (Rous and Beard, 1935). More recent observations suggest that a similar relationship could exist in humans infected with certain types of papillomaviruses (HPV) (Gissmann, 1984). The nature of the host-virus interactions leading to persistence of papillomavirus infections are poorly understood as are the factors leading to the development of virus-associated malignant disease. In addition to in-tracellular events controlling virus replication, lesion formation appears to be controlled, in part, by host immune responses. It is our intent in this paper to portray the nature of persistence of human papillomaviruses and to review the role of immune factors in controlling the diseases induced by these viruses.

Adult inbred MHA hamsters are susceptible to lethal infections with Pichinde virus while inbred LSH hamsters resist such infections. Previous studies demonstrated higher levels of endogenous and induced natural killer (NK) activity in MHA splenocytes than in LSH splenocytes. Preferential replication of Pichinde virus in cells with NK activity was suggested by showing that the greater numbers of infected spleen cells observed in MHA hamsters could be accounted for by a cell population that cosedimented with a peak of NK activity. Increased cellularity of thymi and spleens as well as increased cells sensitive to lymphokines was also found in MHA hamsters as compared to LSH hamsters. In the present study we found that injection of anti-asialo GM1 serum reduced NK activity but did not alter susceptibility to virus infection. However, MHA hamsters were found to be relatively deficient in the production of interleukin 2 and injection of interleukin 2 altered the mortality of hamsters infected with Pichinde virus. These findings suggest that susceptibility to lethal infection by Pichinde virus is associated with reduced ability to produce interleukin 2 in MHA hamsters.

The incidence of cervical cancer has been found to vary between populations. Risk factors of cervical cancer include early age at first marriage, multiple marriages and antibodies to herpes simplex virus type 2 (HSV-2). The interrelatedness of these risk factors was examined by comparing data collected from 428 cancer cases and 947 control women selected from 6 populations having standardized cervical cancer incidence rates varying from 9.3 to 85.1 per 100,000. Logistic regression analysis revealed that multiple marriages, early age at first marriage or pregnancy and HSV-2 antibodies were all associated with significant risk when all 3 factors were entered into the model. Cervical cancer incidence rates were best predicted by the occurrence of HSV-2 antibodies among control women. To further assess the relation between cervical cancer rates and HSV-2 antibody, 2,306 additional sera representing an 0.8% random sample of females over 9 years of age residing in the Republic of Panama were assayed for antibodies to the virus, and the occurrence of antibodies was correlated with invasive cervical cancer rates specific to each Province. Data from both the random sample and the other study populations yielded a linear relation between the occurrence of HSV-2 antibodies and the incidence of cervical cancer. An exception was found for women living in Herrera Province, Republic of Panama, who had a higher cancer rate than predicted by HSV-2 antibody occurrence. The data suggested that infection with HSV-2 is a co-variable of venereal factors, although a role for the virus in the genesis of a certain proportion of cervical cancers is not excluded.

A competitive enzyme-linked immunosorbent assay was used to test for human antibodies to antigenic sites on herpes simplex virus (HSV) glycoproteins C and D, which are recognized by mouse monoclonal antibodies. Antibodies capable of blocking the monoclonal antibodies were detected in the human sera, and the inhibition of binding correlated with the histories of herpetic infections. The binding of monoclonal antibody to glycoprotein C of HSV type 2 was inhibited primarily by sera from patients with recurrent herpes genitalis; however, the binding of the monoclonal antibodies to gC of HSV type 1 was inhibited by sera from patients previously infected with either HSV type 1 or HSV type 2. The observations suggest that the antigenic sites defined by the mouse monoclonal antibodies are recognized by the human host.

A prospective study of premature infants admitted to an intensive care neonatal unit was undertaken to evaluate the relative role of blood transfusions and maternal exposure in infections caused by cytomegalovirus (CMV), varicella zoster virus (VZV) and herpes simplex virus (HSV). During the first year of life, 13.7%, 4.8% and 4% of the infants became infected with CMV, VZV and HSV, respectively, as determined by virus isolation or seroconversion. Transfusion in the newborn period did not influence the rates of VZV or HSV infections. A higher rate of CMV infections occurred in transfused (18.8%) than in non-transfused (11%) infants but the difference was not statistically significant. A significant correlation was found between maternal antibody titers and the rate of CMV infection in infants whether or not transfusion occurred. An even stronger association was found between breast feeding and CMV infections. The risk of alloimmunization to erythrocyte and leucocyte antigens was also assessed; no evidence of increased alloimmunization to these antigens was associated with transfusion.

A double-antibody enzyme immunoassay was developed for the identification and typing of herpes simplex virus (HSV) by employing a polyclonal rabbit capture antiserum together with type-common and type 2-specific monoclonal antibodies as detectors. The test successfully identified 45 type I isolates and 30 type 2 isolates as HSVs. Compared with immunofluorescent staining and restriction endonuclease analysis, enzyme immunoassay correctly typed 45 type 1 and 30 type 2 HSV isolates. Enzyme immunoassay was 100% sensitive for identification of HSV as compared with cell culture and 100% specific for typing as compared with immunofluorescence and restriction endonuclease analysis. Electron microscopy analysis suggested that approximately 10(6) virus particles were required for the identification and typing of HSV by enzyme immunoassay.

Monoclonal antibodies to herpes simplex virus type 2 were found to precipitate different numbers of radiolabeled polypeptides from lysates of virus-infected cells. Antibodies directed against two viral glycoproteins were characterized. Antibodies from hybridoma 17 alpha A2 precipitated a 60,000-molecular-weight polypeptide which chased into a 66,000- and 79,000-molecular-weight polypeptide. All three polypeptides labeled in the presence of [3H]glucosamine and had similar tryptic digest maps. The 60,000-molecular-weight polypeptide also chased into a 31,000-molecular-weight species which did not label with [3H]glucosamine. Antibodies from hybridoma 17 beta C2 precipitated a 50,000-molecular-weight polypeptide which chased into a 56,000- and 80,000-molecular weight polypeptide. These polypeptides also shared a similar tryptic digest map and labeled with [3H]glucosamine. Both monoclonal antibodies were herpes simplex virus type 2 specific. The viral proteins precipitated by 17 alpha A2 antibodies had characteristics similar to those reported for glycoprotein E, whereas the proteins precipitated by 17 beta C2 antibodies appeared to represent a glycoprotein not previously described. This glycoprotein should be tentatively designated glycoprotein F.

Super-infection of Pichinde virus-infected cells with vesicular stomatitis virus (VSV) resulted in the production of pseudotype virus which was not neutralized by antiserum to VSV but which was neutralized by antiserum to Pichinde virus. Analysis of pseudotype virus production in relation to the kinetics of replication of Pichinde virus demonstrated that pseudotype virus production occurred when super-infection with VSV was initiated 8 h or more after infecting the cells with Pichinde virus. The quantities of pseudotype virus produced correlated with the quantities of Pichinde virus antigen detected on the surface of the cells both during acute infection and in cells chronically infected with Pichinde virus. The observations indicate that pseudotype of VSV and Pichinde virus are readily formed and that the formation of pseudotype virus may be used to examine the Pichinde virus antigens expressed on the surface of infected cells.

Immune adherence hemagglutination was compared with the complement fixation test as a means of measuring antibodies to varicella-zoster virus. Analysis of acute- and convalescent-phase sera from patients infected with varicella-zoster or with herpes simplex virus showed the immune adherence hemagglutination test to be more sensitive than the complement fixation test, and greater cross-reactivity between the two viruses appeared to be associated with the increased sensitivity. The two assay methods were used to measure antibodies to varicella-zoster virus in 265 sera obtained from patients of different ages as well as sera from 26 patients with leukemia. There were 35 cases where antibodies were detected by immune adherence hemagglutination but not by complement fixation, whereas in five cases the converse was found. Our findings support the contention that immune adherence hemagglutination is the method of choice for detecting antibodies to varicella-zoster virus.