Skip to main content
Top
Published in: Drugs & Aging 12/2001

01-12-2001 | Review Article

Cytomegalovirus and the Aging Population

Author: Professor Vincent C. Emery

Published in: Drugs & Aging | Issue 12/2001

Login to get access

Abstract

Human cytomegalovirus (HCMV) has the largest genome of any virus known to infect man. The virus has evolved many strategies to manipulate the host immune systems and so can remain latent and evade important immune responses. The human host mounts a substantial immune response against the virus, with up to 1% of the virus-specific CD8+ T cells being directed against specific epitopes.
Acquisition of HCMV occurs progressively from an early age, and in developed countries the overall seroprevalence is approximately 60%. In contrast, specific communities such as gay men, lower socioeconomic groups and people residing in developing countries have seroprevalence rates that can exceed 90%.
It is a widely held belief that successful control of viral infections decreases with increasing age because of a reduction in the capacity of the immune system. Studies in aging populations have shown a specific expansion of the CD8+, CD28− and CD57+ subset of cells in patients who are HCMV-seropositive. Prior infection with HCMV has also been associated with a significantly increased number of CD4+ and CD8+ lymphocytes, as well as cells expressing CD56 and HLA-DR. Thus, HCMV infection can cause substantial perturbations in T cell subsets and these effects persist in the aging population.
In the context of solid organ transplantation, older age of both recipients and donors may serve to increase the frequency of donor-positive recipient-positive (D+R+) transplants, which have only a moderate risk of HCMV disease. In the context of HIV infection, age has been a dominant risk factor for progression to AIDS and death. At present, it does not appear that this can be explained by lack of immune control of HCMV in the aging population, although studies have identified prior HCMV infection as a risk factor for AIDS and death independent of age.
We await further investigations to determine whether the immune control of HCMV in the elderly patient is as effective as in the younger adult, and whether this is linked to pathological consequences.
Literature
1.
go back to reference Griffiths PD, Emery VC. Cytomegalovirus. In: Richman D, Whitley R, Hay den F, editors. Clinical virology. New York (NY): Churchill Livingston Inc, 1997: 445–470 Griffiths PD, Emery VC. Cytomegalovirus. In: Richman D, Whitley R, Hay den F, editors. Clinical virology. New York (NY): Churchill Livingston Inc, 1997: 445–470
2.
go back to reference Stagno S. Cytomegalovirus. In: Remington JS, Klein JO, editors. Infectious diseases of the fetus and newborn infant. Philadelphia: W.B. Saunders, 1990: 240–281 Stagno S. Cytomegalovirus. In: Remington JS, Klein JO, editors. Infectious diseases of the fetus and newborn infant. Philadelphia: W.B. Saunders, 1990: 240–281
3.
go back to reference Ho DD, Neumann AU, Perelson AS, et al. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection [see comments]. Nature 1995; 373(6510): 123–6PubMedCrossRef Ho DD, Neumann AU, Perelson AS, et al. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection [see comments]. Nature 1995; 373(6510): 123–6PubMedCrossRef
4.
go back to reference Wei X, Ghosh SK, Taylor ME, et al. Viral dynamics in human immunodeficiency virus type 1 infection [see comments]. Nature 1995; 373: 117–22PubMedCrossRef Wei X, Ghosh SK, Taylor ME, et al. Viral dynamics in human immunodeficiency virus type 1 infection [see comments]. Nature 1995; 373: 117–22PubMedCrossRef
5.
go back to reference Neumann AU, Lam NP, Dahari H, et al. Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy. Science 1998; 282(5386): 103–7PubMedCrossRef Neumann AU, Lam NP, Dahari H, et al. Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy. Science 1998; 282(5386): 103–7PubMedCrossRef
6.
go back to reference Nowak MA, Bonhoeffer S, Hill AM, et al. Viral dynamics in hepatitis B virus infection. Proc Natl Acad Sci USA 1996; 93(9): 4398–402PubMedCrossRef Nowak MA, Bonhoeffer S, Hill AM, et al. Viral dynamics in hepatitis B virus infection. Proc Natl Acad Sci USA 1996; 93(9): 4398–402PubMedCrossRef
7.
go back to reference Emery VC, Cope AV, Bowen EF, et al. The dynamics of human cytomegalovirus replication in vivo. J Exp Med 1999; 190(2): 177–82PubMedCrossRef Emery VC, Cope AV, Bowen EF, et al. The dynamics of human cytomegalovirus replication in vivo. J Exp Med 1999; 190(2): 177–82PubMedCrossRef
8.
go back to reference Emery VC, Sabin CA, Cope AV, et al. Application of viral-load kinetics to identify patients who develop cytomegalovirus disease after transplantation. Lancet 2000; 355(9220): 2032–6PubMedCrossRef Emery VC, Sabin CA, Cope AV, et al. Application of viral-load kinetics to identify patients who develop cytomegalovirus disease after transplantation. Lancet 2000; 355(9220): 2032–6PubMedCrossRef
9.
go back to reference Emery VC. Relative importance of cytomegalovirus load as a risk factor for cytomegalovirus disease in the immunocompromised host. In: Scholz M, Rabenau HF, Doerr HW, et al., editors. CMV-related immunopathology. Frankfurt: Karger, 1998: 288–301 Emery VC. Relative importance of cytomegalovirus load as a risk factor for cytomegalovirus disease in the immunocompromised host. In: Scholz M, Rabenau HF, Doerr HW, et al., editors. CMV-related immunopathology. Frankfurt: Karger, 1998: 288–301
10.
go back to reference Mendez J, Espy M, Smith TF, et al. Clinical significance of viral load in the diagnosis of cytomegalovirus disease after liver transplantation. Transplantation 1998; 65(11): 1477–81PubMedCrossRef Mendez J, Espy M, Smith TF, et al. Clinical significance of viral load in the diagnosis of cytomegalovirus disease after liver transplantation. Transplantation 1998; 65(11): 1477–81PubMedCrossRef
11.
go back to reference Britt WB, Mach M. Human cytomegalovirus glycoproteins. Intervirology 1996; 39(5–6): 401–12PubMed Britt WB, Mach M. Human cytomegalovirus glycoproteins. Intervirology 1996; 39(5–6): 401–12PubMed
12.
go back to reference Wills MR, Carmichael AJ, Mynard K, et al. The human cytotoxic T-lymphocyte (CTL) response to cytomegalovirus is dominated by structural protein pp65: frequency, specificity, and T-cell receptor usage of pp65-specific CTL. J Virol 1996; 70(11): 7569–79PubMed Wills MR, Carmichael AJ, Mynard K, et al. The human cytotoxic T-lymphocyte (CTL) response to cytomegalovirus is dominated by structural protein pp65: frequency, specificity, and T-cell receptor usage of pp65-specific CTL. J Virol 1996; 70(11): 7569–79PubMed
13.
go back to reference Kern F, Surel IP, Faulhaber N, et al. Target structures of the CD8(+)-T-cell response to human cytomegalovirus: the 72-kilodalton major immediate-early protein revisited. J Virol 1999; 73(10): 8179–84PubMed Kern F, Surel IP, Faulhaber N, et al. Target structures of the CD8(+)-T-cell response to human cytomegalovirus: the 72-kilodalton major immediate-early protein revisited. J Virol 1999; 73(10): 8179–84PubMed
14.
go back to reference Boppana SB, Britt WJ. Antiviral antibody responses and intrauterine transmission after primary maternal cytomegalovirus infection. J Infect Dis 1995; 171(5): 1115–21PubMedCrossRef Boppana SB, Britt WJ. Antiviral antibody responses and intrauterine transmission after primary maternal cytomegalovirus infection. J Infect Dis 1995; 171(5): 1115–21PubMedCrossRef
15.
go back to reference Hassan-Walker AF, Vargas Cuero AL, Mattes FM, et al. CD8 cytotoxic lymphocyte responses against cytomegalovirus following liver transplantation: correlation with time from transplant and receipt of tacrolimus. J Infect Dis 2001; 183:835–43PubMedCrossRef Hassan-Walker AF, Vargas Cuero AL, Mattes FM, et al. CD8 cytotoxic lymphocyte responses against cytomegalovirus following liver transplantation: correlation with time from transplant and receipt of tacrolimus. J Infect Dis 2001; 183:835–43PubMedCrossRef
16.
go back to reference Singhai S, Shaw JC, Ainsworth J, et al. Direct visualization and quantitation of cytomegalovirus-specific CD8+ cytotoxic T-lymphocytes in liver transplant patients [see comments]. Transplantation 2000; 69(11): 2251–9CrossRef Singhai S, Shaw JC, Ainsworth J, et al. Direct visualization and quantitation of cytomegalovirus-specific CD8+ cytotoxic T-lymphocytes in liver transplant patients [see comments]. Transplantation 2000; 69(11): 2251–9CrossRef
17.
go back to reference Engstrand M, Tournay C, Peyrat MA, et al. Characterization of CMVpp65-specific CD8+ T lymphocytes using MHC tetramers in kidney transplant patients and healthy participants. Transplantation 2000; 69(11): 2243–50PubMedCrossRef Engstrand M, Tournay C, Peyrat MA, et al. Characterization of CMVpp65-specific CD8+ T lymphocytes using MHC tetramers in kidney transplant patients and healthy participants. Transplantation 2000; 69(11): 2243–50PubMedCrossRef
18.
go back to reference Reynolds DW, Stagno S, Stubbs KG, et al. Inapparent congenital cytomegalovirus infection with elevated cord IgM levels. Casual relation with auditory and mental deficiency. N Engl J Med 1974; 290(6): 291–6PubMedCrossRef Reynolds DW, Stagno S, Stubbs KG, et al. Inapparent congenital cytomegalovirus infection with elevated cord IgM levels. Casual relation with auditory and mental deficiency. N Engl J Med 1974; 290(6): 291–6PubMedCrossRef
19.
go back to reference Deayton J, Mocroft A, Wilson P, et al. Loss of cytomegalovirus (CMV) viraemia following highly active antiretroviral therapy in the absence of specific anti-CMV therapy. AIDS 1999; 13(10): 1203–6PubMedCrossRef Deayton J, Mocroft A, Wilson P, et al. Loss of cytomegalovirus (CMV) viraemia following highly active antiretroviral therapy in the absence of specific anti-CMV therapy. AIDS 1999; 13(10): 1203–6PubMedCrossRef
20.
go back to reference Deayton JR, Wilson P, Sabin CA, et al. Changes in the natural history of cytomegalovirus retinitis following the introduction of highly active antiretroviral therapy [in process citation]. AIDS 2000; 14(9): 1163–70PubMedCrossRef Deayton JR, Wilson P, Sabin CA, et al. Changes in the natural history of cytomegalovirus retinitis following the introduction of highly active antiretroviral therapy [in process citation]. AIDS 2000; 14(9): 1163–70PubMedCrossRef
21.
go back to reference Autran B, Carcelaint G, Li TS, et al. Restoration of the immune system with anti-retroviral therapy. Immunol Lett 1999; 66(1–3): 207–11PubMedCrossRef Autran B, Carcelaint G, Li TS, et al. Restoration of the immune system with anti-retroviral therapy. Immunol Lett 1999; 66(1–3): 207–11PubMedCrossRef
22.
go back to reference Stagno S, Reynolds DW, Pass RF, et al. Breast milk and the risk of cytomegalovirus infection. N Engl J Med 1980; 302(19): 1073–6PubMedCrossRef Stagno S, Reynolds DW, Pass RF, et al. Breast milk and the risk of cytomegalovirus infection. N Engl J Med 1980; 302(19): 1073–6PubMedCrossRef
23.
go back to reference Stagno S. Cytomegalovirus. In: Rimington JS, Klein JO, editors. Infectious diseases of the fetus and newborn infant. Philadephia: W.B. Saunders, 1990: 240–81 Stagno S. Cytomegalovirus. In: Rimington JS, Klein JO, editors. Infectious diseases of the fetus and newborn infant. Philadephia: W.B. Saunders, 1990: 240–81
24.
go back to reference Griffiths PD, Baboonian C, Rutter D, et al. Congenital and maternal cytomegalovirus infections in a London population. Br J Obstet Gynaecol 1991; 98(2): 135–40PubMedCrossRef Griffiths PD, Baboonian C, Rutter D, et al. Congenital and maternal cytomegalovirus infections in a London population. Br J Obstet Gynaecol 1991; 98(2): 135–40PubMedCrossRef
25.
go back to reference Griffiths PD, Baboonian C. A prospective study of primary cytomegalovirus infection during pregnancy: final report. Br J Obstet Gynaecol 1984; 91: 307–15PubMedCrossRef Griffiths PD, Baboonian C. A prospective study of primary cytomegalovirus infection during pregnancy: final report. Br J Obstet Gynaecol 1984; 91: 307–15PubMedCrossRef
26.
go back to reference Doria G, Frasca D. Genes, immunity, and senescence: looking for a link. Immunol Rev 1997; 160: 159–70PubMedCrossRef Doria G, Frasca D. Genes, immunity, and senescence: looking for a link. Immunol Rev 1997; 160: 159–70PubMedCrossRef
27.
go back to reference Schmader K. Herpes zoster in the elderly: issues related to geriatrics. Clin Infect Dis 1999; 28(4): 736–9PubMedCrossRef Schmader K. Herpes zoster in the elderly: issues related to geriatrics. Clin Infect Dis 1999; 28(4): 736–9PubMedCrossRef
28.
go back to reference Merino J, Martinez-Gonzalez MA, Rubio M, et al. Progressive decrease of CD8high+ CD28+CD57 -cells with ageing. Clin Exp Immunol 1998; 112(1): 48–51PubMedCrossRef Merino J, Martinez-Gonzalez MA, Rubio M, et al. Progressive decrease of CD8high+ CD28+CD57 -cells with ageing. Clin Exp Immunol 1998; 112(1): 48–51PubMedCrossRef
29.
go back to reference Looney RJ, Falsey A, Campbell D, et al. Role of cytomegalovirus in the T cell changes seen in elderly individuals. Clin Immunol 1999; 90(2): 213–9PubMedCrossRef Looney RJ, Falsey A, Campbell D, et al. Role of cytomegalovirus in the T cell changes seen in elderly individuals. Clin Immunol 1999; 90(2): 213–9PubMedCrossRef
30.
go back to reference Schmader KE, Rahija R, Porter KR, et al. Aging and reactivation of latent murine cytomegalovirus. J Infect Dis 1992; 166(6): 1403–7PubMedCrossRef Schmader KE, Rahija R, Porter KR, et al. Aging and reactivation of latent murine cytomegalovirus. J Infect Dis 1992; 166(6): 1403–7PubMedCrossRef
32.
go back to reference Valantine HA, Gao S-Z, Menon SG, et al. Impact of prophylactic immediate posttransplant ganciclovir on development of transplant atherosclerosis: A post-hoc analysis of a randomised, placebo-controlled study. Circulation 1999; 100: 61–6PubMedCrossRef Valantine HA, Gao S-Z, Menon SG, et al. Impact of prophylactic immediate posttransplant ganciclovir on development of transplant atherosclerosis: A post-hoc analysis of a randomised, placebo-controlled study. Circulation 1999; 100: 61–6PubMedCrossRef
33.
go back to reference Evans PC, Soin A, Wreghitt TG, et al. An association between cytomegalovirus infection and chronic rejection after liver transplantation. Transplantation 2000; 69(1): 30–5PubMedCrossRef Evans PC, Soin A, Wreghitt TG, et al. An association between cytomegalovirus infection and chronic rejection after liver transplantation. Transplantation 2000; 69(1): 30–5PubMedCrossRef
34.
go back to reference Lowance D, Neumayer H-H, Legendre C, et al. Valaciclovir reduces the incidence of cytomegalovirus disease and acute rejection in renal allograft recipients. N Engl J Med 1999; 340: 1462–70PubMedCrossRef Lowance D, Neumayer H-H, Legendre C, et al. Valaciclovir reduces the incidence of cytomegalovirus disease and acute rejection in renal allograft recipients. N Engl J Med 1999; 340: 1462–70PubMedCrossRef
35.
go back to reference Griffiths PD, Ait-Khaled M, Bearcroft C, et al. Human herpesviruses 6 and 7 as potential pathogens after liver transplant: prospective comparison with the effect of cytomegalovirus. J Med Virol 1999; 59: 496–501PubMedCrossRef Griffiths PD, Ait-Khaled M, Bearcroft C, et al. Human herpesviruses 6 and 7 as potential pathogens after liver transplant: prospective comparison with the effect of cytomegalovirus. J Med Virol 1999; 59: 496–501PubMedCrossRef
36.
go back to reference Phillips AN, Lee CA, Elford J, et al. More rapid progression to AIDS in older HIV-infected people: the role of CD4+ T-cell counts. J Acquir Immune Defic Syndr 1991; 4: 970–5PubMed Phillips AN, Lee CA, Elford J, et al. More rapid progression to AIDS in older HIV-infected people: the role of CD4+ T-cell counts. J Acquir Immune Defic Syndr 1991; 4: 970–5PubMed
37.
go back to reference Spector SA, Hirata KK, Newman TR. Identification of multiple cytomegalovirus strains in homosexual men with acquired immunodeficiency syndrome. J Infect Dis 1984; 150(6): 953–6PubMedCrossRef Spector SA, Hirata KK, Newman TR. Identification of multiple cytomegalovirus strains in homosexual men with acquired immunodeficiency syndrome. J Infect Dis 1984; 150(6): 953–6PubMedCrossRef
Metadata
Title
Cytomegalovirus and the Aging Population
Author
Professor Vincent C. Emery
Publication date
01-12-2001
Publisher
Springer International Publishing
Published in
Drugs & Aging / Issue 12/2001
Print ISSN: 1170-229X
Electronic ISSN: 1179-1969
DOI
https://doi.org/10.2165/00002512-200118120-00004

Other articles of this Issue 12/2001

Drugs & Aging 12/2001 Go to the issue

Adis New Drug Profile

Tegafur/Uracil

Adis New Drug Profile

Oral Tegafur/Uracil

Adis New Drug Profile

Tegafur/Uracil

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.