Infection and immunoregulation of T lymphocytes by parainfluenza virus type 3.

Abstract

Human paanfluenza virus type 3 (HPIV3) is a major cause of dise In newborns and Infants. It also has a king potential to reinfect individuals throughout their lives, suggesting that HPIV3 does not induce lifelong immunity; however, the operative mechanism for the failure to prevent reinfection is not known. We have as d the potential of the virus to infect nontransformed human Tlymphocytes and have found that T cells are readily infected by the virus. Productive infection requires activation of the T cells and results in a marked inhibition of proliferation. Furthermore, our results indicate that exposure to the virus, even without overt expression of viral proteins as det by imunohistol, profoundly alters the functional capacity of the T cells. The capacity of the virus to regulate T-lymphocyte function may play an important role In the failure of the virus to induce lifelong immunity.Human parainfluenza virus type 3 (HPIV3) causes severe respiratory tract infections in infants and children (1-5) and upper respiratory tract infections in adults (6-8). It is efficiently spread from person-to-person (5, 6); consequently, all adults possess anti-HPIV3 immunoglobulins (6).Persistent infection of the virus has been documented in various clinical situations (8-10). Moreover, reinfection after a primary infection with HPIV3 is a common occurrence (1,6). In one study the frequency of HPIV3 reinfection was found to be 58% in 1-year-old children and 34% in 2-year-old children (1). Even in the presence of circulating neutralizing antibodies, adults have been shown to be susceptible to reinfection (6). This clinical characteristic is distinct from infection with either measles or mumps viruses, which result in lifelong immunity against reinfection. It appears that infection with HPIV3 does not result in the establishment of a state of long-lasting immunity (11).The mechanisms for persistent infection or for reinfection with HPIV3 have not been determined; however, it is likely that the equilibrium between the human host and the viral parasite arises as a result ofthe complex interactions between the host's immune system and the virus. One significant aspect of this interaction is infection of T lymphocytes by viruses. Viral infection of T lymphocytes has been demonstrated for many different viruses and has been shown to profoundly alter the immune response (12-15). Although T cells have the potential to lyse virally infected cells, help B lymphocytes produce immunoglobulins, and establish longlived memory cells, the possibility that HPIV3-mediated immunoregulation of T lymphocytes plays a role in either persistence or reinfection has not been considered.In this report we demonstrate that HPIV3 has a marked immunoregulatory effect on human T lymphocytes even in the absence of productive infection as detected by immunohistology. Experiments were also performed by infecting the PBMC with HPIV3 without washing out the virus. The results from these experiments were similar to the results from experiments that were perfo...

Alpha and Lambda Interferon Together Mediate Suppression of CD4 T Cells Induced by Respiratory Syncytial Virus

“…Figure 2A shows that RSV and not influenza virus inhibits proliferation of T cells in response to SEB. Exposure of MDDC to PIV3, another paramyxovirus, modestly inhibited T-cell proliferation as previously reported (54,55). To simplify the experimental system, we mixed purified CD4 T cells (97 to 99% pure, not shown) with RSVexposed MDDC and found suppression to be essentially the same (Fig.…”

“…The mechanism by which measles suppresses T-cell responses is not clear, but altered cytokine expression and impaired antigen presentation have been implicated (for reviews, see references 35 and 50). PIV3 is also immunosuppressive, perhaps a consequence of increased expression of interleulin-10 (IL-10) (54,55).…”

“…Among Paramyxoviridae family members, RSV, PIV3, and measles are known to suppress T-cell responses to secondary antigenic stimuli (43,45,50,55). Clinical immunosuppression is a common complication of measles, and secondary bacterial and viral infections contribute to its high morbidity and mortality (6).…”

Natural Killer Cells Regulate T-Cell Proliferation during Human Parainfluenza Virus Type 3 Infection

“…Reinfection is a common occurrence (13,15). This clinical characteristic is distinct from infection with most viral infections, such as measles, mumps (15), and subtype-specific influenza (6), which, in most cases, result in lifelong immunity against reinfection with the same strain. Even in the presence of circulating neutralizing antibodies, individuals have been shown to be susceptible to reinfection (3).…”

Polarity of Human Parainfluenza Virus Type 3 Infection in Polarized Human Lung Epithelial A549 Cells: Role of Microfilament and Microtubule

“…2A) suggest that a small proportion of basolaterally released virus, in the absence of innate immune defense, can propagate itself in the systemic circulation to infect non-respiratory-tract cells. Moreover, infection of T lymphocytes with HPIV-3 was shown to be important for immunoregulation of these cells that leads to the failure to induce lifelong immunity against the virus (22). Since T lymphocytes are selectively localized in the basolateral surfaces of epithelial cells following infiltration from the systemic circulation (3), the basolaterally derived HPIV-3 could also infect T lymphocytes at this site to modulate the immunoregulation mechanism of these cells.…”